• Humans
• Carcinoma, Non-Small-Cell Lung/surgery
• Carcinoma, Non-Small-Cell Lung/immunology
• Carcinoma, Non-Small-Cell Lung/pathology
• Female
• Male
• Lung Neoplasms/surgery
• Lung Neoplasms/pathology
• Lung Neoplasms/immunology
• Middle Aged
• Aged
• Lymphatic Metastasis
• Retrospective Studies
• Lymph Node Excision
• Pneumonectomy
• Lymph Nodes/pathology
• Inflammation/immunology

• LMR
• PLR
• immunotherapy
• irAEs
• lung adenocarcinoma
• prognosis

• Humans
• Male
• Female
• Adenocarcinoma of Lung/drug therapy
• Adenocarcinoma of Lung/blood
• Adenocarcinoma of Lung/mortality
• Adenocarcinoma of Lung/pathology
• Adenocarcinoma of Lung/immunology
• Adenocarcinoma of Lung/genetics
• Lung Neoplasms/drug therapy
• Lung Neoplasms/blood
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Lung Neoplasms/immunology
• Middle Aged
• Aged
• Prognosis
• Retrospective Studies
• Biomarkers, Tumor/blood
• Neoplasm Staging
• Immune Checkpoint Inhibitors/adverse effects
• Immune Checkpoint Inhibitors/therapeutic use
• Adult
• Aged, 80 and over

• Lung function
• NSCLC
• Prognosis
• Systemic inflammatory response
• Testin

• Humans
• Carcinoma, Non-Small-Cell Lung/pathology
• Forced Expiratory Volume
• Lung/pathology
• Lung Neoplasms/pathology
• Prognosis
• Pulmonary Disease, Chronic Obstructive/diagnosis
• Spirometry
• Systemic Inflammatory Response Syndrome

• 81902354 National Natural Science Foundation of China

• lymphocyte-to-monocyte ratio
• prognostic markers
• tongue squamous cell carcinoma

• circulating tumor (ctDNA)
• circulating tumor cell (CTC)
• immunotherapy
• liquid biopsy
• neutrophil lymphocyte ratio (NLR)
• non-small cell lung cancer (NSCLC)
• soluble biomarkers

• Université de Reims Champagne-Ardenne
• Institut National de la Santé et de la Recherche Médicale

• Mice
• Animals
• Receptors, Immunologic/metabolism
• Carcinoma, Non-Small-Cell Lung/metabolism
• Lung Neoplasms/metabolism
• Blood Platelets/metabolism
• CD8-Positive T-Lymphocytes

• R01 HL115247 NHLBI NIH HHS
• R01 HL122815 NHLBI NIH HHS
• R01 HL150515 NHLBI NIH HHS
• UL1 TR001863 NCATS NIH HHS

Due to its effectiveness, cancer immunotherapy has attracted widespread attention from clinicians and scientific researchers. Numerous studies have proven that effective stratification of cancer patients would promote the personalized application of immunotherapy. Therefore, we used the transcriptome data of nearly 1,000 patients with non-small cell lung cancer (NSCLC) to construct a new immune subgroup. We found that the new immune subgroup, named cluster 2, was a mixture of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and showed poor overall survival, which was further verified in the independent validation set. Immune infiltration correlation analysis showed that the Mast cell type and its status subdivisions had a predictive effect on the prognosis of NSCLC, especially in LUAD. Phenotypic analysis suggested that epithelial-mesenchymal transition (EMT) was positively correlated with immunosuppression, supporting the correlation between tumor phenotype and immune background. Although immune subtypes failed to significantly distinguish the progression-free survival (PFS) of immunotherapy patients, they showed the expected trend; the sample size needs to be further expanded for verification. In addition, some results indicated that the two cancer types, LUAD and LUSC, might require independent analyses.

• NSCLC
• immune subgroup
• prognosis
• therapeutic efficacy

• inflammation
• monocyte
• prognosis
• solid tumor

We evaluated the prognostic potential of tumor ¹⁸F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy.

A total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response.

Patients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001).

Pre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.

• Lymphocyte-monocyte ratio
• Maximum standardized uptake value
• Non-small cell lung cancer
• Response
• Survival

• immunotherapy
• lung cancer
• lymphocyte-to-monocyte ratio
• meta-analysis
• prognosis

• Biomarkers
• Humans
• Leukocyte Count
• Lung Neoplasms/blood
• Lung Neoplasms/diagnosis
• Lung Neoplasms/mortality
• Lung Neoplasms/therapy
• Lymphocyte Count
• Lymphocytes
• Monocytes
• Prognosis
• Proportional Hazards Models
• Publication Bias

Inflammatory biomarkers have been associated with clinical outcomes in non-small cell lung cancer (NSCLC). However, the best prognostic marker(s) has not been identified, and the association between inflammatory markers and clinical characteristics is poorly understood. We selected 1,237 patients with resected NSCLC from Kyushu University (2003–2015) and Kyushu Cancer Center (2009–2015) in Japan. Pearson product-moment correlation coefficient among inflammatory markers and area under curve (AUC) of receiver operating characteristic (ROC) curve analyses for overall survival (OS) were calculated. We analyzed the associations between inflammatory markers and clinical factors using Student’s t-test. Univariate and multivariate analyses with Cox proportional hazards regression analyses were performed to evaluate the relationship between survival and clinical factors. The cut-off values for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio, and derived NLR (dNLR) were determined by ROC curve analyses for OS. We found a strong positive correlation between NLR and dNLR (r = 0.9629). The AUC of LMR was the highest amongst the measured metrics, and the AUC of NLR was higher than dNLR. Levels of some inflammatory markers were associated with sex, smoking, squamous cell carcinoma, and pathological stage. LMR ≥ 5.11 and lactate dehydrogenase (LDH) concentration ≥ 222 (U/L) were independent predictors of both disease-free survival (DFS) and OS (LMR; P = 0.0009 and 0.0008, LDH; P = 0.0195 and 0.0187, respectively). Certain inflammatory markers, potentially linked to smoking, were associated with an advanced pathological stage in NSCLC. LMR and LDH were independent predictors of both DFS and OS.

This study was designed to investigate the prognostic value of the lymphocyte to monocyte ratio (LMR) in patients with gallbladder carcinoma (GBC).

We retrospectively enrolled 154 consecutive GBC patients from 2005 to 2017 in this study. The LMR of preoperative blood samples was calculated by dividing the lymphocyte count by the monocyte count. A receiver operating characteristic (ROC) curve was employed to identify the optimal cut-off value of the LMR in the determination of overall survival (OS). The Kaplan–Meier method was utilized to assess OS, and the Log rank test was employed to compare survival differences. Univariate and multivariate Cox regression analyses were conducted to detect independent prognostic indicators.

The optimal cut-off point for the LMR was 4.76 according to the ROC curve. Patients ≤60 years old with an LMR ≤4.76 experienced significantly worse OS than those with an LMR >4.76 (hazard ratio (HR): 0.399, 95% confidence interval (CI): 0.265–0.602, P<0.001); however, the prognostic value of the LMR was not determined in patients >60 years old or among the entire study cohort (both P>0.05). Significantly poorer OS was observed in patients >60 years with an LMR ≤4.21 compared to those with an LMR >4.21 (HR: 1.830, 95% CI: 1.129–2.967, P=0.014). Multivariate Cox regression analysis indicated that both the high and low LMR cut-off values were independent risk factors for OS (HR: 0.272, 95% CI: 0.105–0.704, P=0.007; HR: 0.544, 95% CI: 0.330–0.895, P=0.017).

The LMR is an independent prognostic indicator for GBC patients, the cut-off value of which is age dependent.

• LMR
• biomarker
• gallbladder cancer
• lymphocyte to monocyte ratio
• prognosis
• survival

• Nivolumab
• Non-small cell lung cancer
• Pembrolizumab
• Predictive factor
• Prognostic factor
• Serum markers

• Antineoplastic Agents, Immunological/therapeutic use
• Biomarkers
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Humans
• Lung Neoplasms/drug therapy
• Neoplasm Recurrence, Local
• Prognosis

The prognosis of patients with stage I non-small cell lung cancer (NSCLC) is often uncertain. This study aims to investigate a new prognostic tool to classify stage I NSCLC patients more accurately.

CD68 and CD163 macrophages were quantified by immunohistochemical analyses of the center of the tumor and the invasive margin of the 339 tumors, which were used to construct the macrophage immunoscore (MI). Cox proportional hazards models determined the effects of multiple factors on disease-free survival (DFS) and overall survival (OS). One nomogram was developed to predict DFS and OS of stage I patients.

The multivariate Cox analysis identified MI (P<0.001), lymphocyte-to-monocyte ratio (LMR, P=0.006), and TNM stage (P=0.046) as independent prognostic factors for DFS. Compared with MI, TNM stage, and LMR alone, the nomogram improved the prediction accuracy of both DFS and OS in terms of the Harrell concordance index in the training cohort (0.812, P<0.001 for DFS; 0.810, P<0.001 for OS) and the external validation cohort (0.796, P<0.001 for DFS; 0.791, P<0.001 for OS). In addition, net reclassification (Nomogram vs. TNM-stage, P<0.001 for DFS and OS) and the integrated discrimination (Nomogram vs. TNM stage, P<0.001 for DFS and OS) also validated this improvement.

The immunoscore-based prognostic nomogram could effectively predict DFS and OS of stage I NSCLC patients and enhance the predictive value of the TNM stage system.

• Non-small cell lung cancer (NSCLC)
• immunoscore
• lymphocyte-to-monocyte ratio (LMR)

• Prognostic
• biomarker
• lung cancer

• cancer immunology
• innate immunity
• monocytes
• myeloid cell heterogeneity
• neutrophils
• tumor microenvironment

• Animals
• Cell Differentiation/immunology
• Dendritic Cells/immunology
• Disease Progression
• Endothelial Cells/immunology
• Humans
• Immunity, Innate/immunology
• Macrophages/immunology
• Mice
• Monocytes/cytology
• Monocytes/immunology
• Neoplasms/immunology
• Neutrophils/immunology
• Tumor Microenvironment/immunology

• Lymphocyte-to-monocyte ratio
• Meta-analysis
• Non-small cell lung cancer
• Prognosis

There is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment.

We searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.

A total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR = 0.578, 95% CI 0.522–0.641, P < 0.001) and PFS (HR = 0.598, 95% CI 0.465–0.768, P < 0.001). The effect of LMR on OS was observed among various tumor types. A higher pretreatment LMR was associated with improved OS in chemotherapy (n = 10, HR = 0.592, 95% CI 0.518–0.676, P < 0.001), surgery (n = 10, HR = 0.683, 95% CI 0.579–0.807, P < 0.001) and combined therapy (n = 11, HR = 0.507, 95% CI 0.442–0.582, P < 0.001) in the subgroup analysis by different therapeutic strategies. The cut-off value for LMR was 3.0 (range = 2.35–5.46). Subgroup analysis according to the cut-off value showed a significant prognostic value of LMR on OS and PFS in both subgroups.

A high pretreatment LMR is associated with favorable clinical outcomes in advanced-stage epithelial cancers undergoing different therapeutic strategies. LMR could be used to improve clinical decision-making regarding treatment in advanced epithelial cancers.

The online version of this article (10.1186/s12935-018-0698-5) contains supplementary material, which is available to authorized users.

• Epithelial cancer
• Lymphocyte-to-monocyte ratio
• Prognosis
• Treatment

To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI).

One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either EGFR exon 19 deletion (E19del) or EGFR exon 21 L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers. The Kaplan–Meier statistics and Cox regression model were used to test the differences of progression-free survival (PFS) between groups by the optimal cutoff point of biomarkers.

The median values of white blood cell (WBC), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) in NSCLC patients tended to be reduced after 3 months treated with EGFR TKI and increased conversely when the disease develops progression (P<0.001). With an optimal cutoff point of 2.96, NLR is the best prognostic marker in prediction of clinical response among the investigated markers (area under the curve [AUC]=0.873, 95% CI: 0.821–0.926, P<0.001), and it is an independent predictive marker (OR=3.52, 95% CI: 1.42–8.71, P<0.001). With optimal cutoff point of 0.38, MLR is also a predictive marker in response evaluation (AUC=0.762, 95% CI: 0.691–0.832). Univariate analyses have shown that the larger tumor size (>3cm) and the high level of pretreatment NLR were associated with the shortening of PFS (HR=2.24, 95% CI: 1.04–4.83, P=0.039 and HR=2.67, 95% CI: 1.41–5.03, P=0.006, respectively). Multivariate analysis has shown that the elevated NLR is an independent prognostic marker for worse PFS of NSCLC patients treated with EGFR TKI (HR=2.15, 95% CI: 1.15–3.99, P=0.016).

NLR and MLR are valuable markers in response evaluation for NSCLC patients treated with EGFR TKI. The elevated NLR is also an independent prognostic factor for worse survival.

• EGFR TKI
• NLR
• NSCLC
• neutrophil to lymphocyte ratio

Research indicates that the presence of a systemic inflammatory response plays an important role in predicting survival in patients with cancer. The aim of this study was to investigate the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index, and the combination of preoperative LMR and PLR (LMR-PLR) in predicting the survival of patients with stage IB non-small-cell lung cancer (NSCLC).

We retrospectively analyzed clinical data of 577 patients with stage IB NSCLC who underwent pneumonectomy from January 1999 to December 2009. Univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including LMR-PLR. The cutoff values for LMR and PLR were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cutoff values of LMR and PLR were 3.16 and 81.07, respectively. We divided the patients into three groups according to their LMR and PLR status and defined them with different scores. Patients with both high LMR (>3.16) and low PLR (≤81.07) were given a score of 2, whereas those with one or neither were scored 1 or 0, respectively. Survival curves were plotted using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards analyses were used to identify the factors associated with overall survival (OS).

The median follow-up time was 93.77 months. The allocation of the LMR-PLR score was as follows: LMR-PLR = 0, 193 (33.4%) patients; LMR-PLR = 1, 308 (53.4%) patients; and LMR-PLR = 2, 76 (13.2%) patients. After multivariate analysis, our results showed that LMR-PLR was an independent prognostic indicator for OS (P=0.001). The 10-year OS rates were 70.0%, 60.4%, and 49.5% for LMR-PLR =2, LMR-PLR =1, and LMR-PLR =0, respectively (P<0.001).

This study demonstrated that preoperative LMR and PLR are simple, readily available, and low-cost biomarkers. Preoperative LMR-PLR score can be used as a valuable prognostic marker for long-term survival in stage IB NSCLC patients who underwent surgery.

• IB non-small-cell lung cancer
• lymphocyte-to-mono-cyte ratio
• platelet-to-lymphocyte ratio
• pneumonectomy
• prognostic factors
• systemic inflammation

A combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet.

In this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment.

Between January 2012 and July 2016, 217 patients with stage IV NSCLC and MPE undergoing active anticancer treatment were selected for evaluation. If patients had both low LMR (< 2.47) and increased platelet (> 30.0 ×10⁴ mm-3), they were assigned to COP-LMR group 2. Patients with one parameter were assigned to COP-LMR group 1. If none, patients were assigned to COP-LMR group 0.

Median overall survival (OS) (P < 0.001), progression free survival (PFS) (P < 0.001) and histological feature (P = 0.003) showed significant differences among COP-LMR groups. For COP-LMR groups 0, 1 and 2, median survival times were 35.9, 14.7 and 7.4 months, respectively, while median progression free times were 19.2, 13.3 and 7.4 months, respectively. Older age, male, low albumin, high CRP and high COP-LMR (0 vs 1, P = 0.021, hazard ratio (HR): 1.822, 95% confidence interval (CI): 1.096–3.027 and 0 vs 2, P = 0.003, HR: 2.464, 95% CI: 1.373–4.421) were independent predictive factors for shorter OS. Age, sex, histology, albumin, or CRP had no significant influence on PFS. High COP-LMR was the significant factor in predicting shorter PFS (0 vs 1, P = 0.116 and 0 vs 2, P = 0.007, HR: 1.902, 95% CI: 1.194–3.028).

A combination of pretreatment LMR and platelet levels can be used to predict short survival in stage IV NSCLC patients who underwent active anticancer treatment.

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/blood
• Carcinoma, Non-Small-Cell Lung/complications
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/mortality
• Cohort Studies
• Female
• Humans
• Leukocyte Count
• Lung Neoplasms/blood
• Lung Neoplasms/complications
• Lung Neoplasms/drug therapy
• Lung Neoplasms/mortality
• Male
• Middle Aged
• Neoplasm Staging
• Platelet Count
• Pleural Effusion, Malignant/blood
• Pleural Effusion, Malignant/etiology
• Pleural Effusion, Malignant/mortality
• Pleural Effusion, Malignant/therapy
• Prognosis

Emerging inflammatory response biomarkers are developed to predict the survival of patients with cancer, the aim of our study is to establish an inflammation-related nomogram based on the classical predictive biomarkers to predict the survivals of patients with non-small cell lung cancer (NSCLC).

Nine hundred and fifty-two NSCLC patients with lung cancer surgery performed were enrolled into this study. The cutoffs of inflammatory response biomarkers were determined by Receiver operating curve (ROC). Univariate and multivariate analysis were conducted to select independent prognostic factors to develop the nomogram.

The median follow-up time was 40.0 months (range, 1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P = 0.045) was selected to establish the nomogram which could predict the 5-year OS probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve displayed an optimal agreement between the actual observed outcomes and the predictive results.

Neutrophil to lymphocyte ratio was shown to be a valuable biomarker for predicting survival of patients with NSCLC. The addition of neutrophil to lymphocyte ratio could improve the accuracy and predictability of the nomogram in order to provide reference for clinicians to assess patient outcomes.

• Inflammatory response biomarker
• Nomogram
• Non-small cell lung cancer

• advanced
• non-small-cell lung cancer
• prognostic
• systemic immune-inflammation index

• Head and neck cancer
• Inflammatory markers
• LMR
• Lymphocyte–monocyte ratio
• Meta-analysis
• Prognosis
• Systematic review

Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR) and modified Glasgow prognostic score (mGPS) are useful prognostic markers based on host-related systemic inflammatory response. They have been shown as independent prognostic biomarkers in various cancers, including non-small cell lung cancer. However, there has been little evidence for a specific population of pulmonary adenocarcinoma without active epidermal growth factor receptor (EGFR) mutation.

We retrospectively reviewed 159 patients who met the following criteria: histologically or cytologically diagnosed adenocarcinoma, confirmed wild-type EGFR, started first-line cytotoxic chemotherapy between July 2007 and March 2017 at our hospital, and c-stage IIIB or IV. We compared overall survival (OS) between dichotomized groups by the optimal cut-off points of NLR and LMR, and mGPS 0 - 1 vs. 2. Univariate and multivariate Cox proportional hazard analyses also detected prognostic factors for OS.

As favorable prognostic factors for OS, multivariate analysis detected Eastern Cooperative Oncology Group performance status (ECOG PS) 0 - 1 (hazard ratio (HR) 3.43, 95% confidence interval (CI): 2.12 - 5.53; P < 0.01), LMR ≥ 1.97 (HR 0.39, 95% CI: 0.21 - 0.72; P < 0.01) and mGPS 0 - 1 (HR 1.95, 95% CI: 1.20 - 3.16; P < 0.01). The OS of LMR ≥ 1.97 and mGPS 0 - 1 groups were significantly longer than those of LMR < 1.97 and mGPS 2 groups, respectively. We divided 159 patients into three groups, both LMR ≥ 1.97 and mGPS 0 - 1, either LMR ≥ 1.97 or mGPS 0 - 1 and both LMR < 1.97 and mGPS 2. The OS of both LMR < 1.97 and mGPS 2 was significantly shorter than the other two groups. After adjustment for age, sex, ECOG PS, sodium, alkaline phosphatase and NLR, multivariate analysis found both LMR < 1.97 and mGPS 2 as an independent poor prognostic combination in comparison with both LMR ≥ 1.97 and mGPS0-1 (HR 5.98, 95% CI: 2.64 - 13.5; P < 0.01).

LMR and mGPS are independent prognostic markers for pulmonary adenocarcinoma with wild-type EGFR. Combination of LMR and mGPS can stratify patients according to prognosis.

• Adenocarcinoma
• Chemotherapy
• Lymphocyte to monocyte ratio
• Modified Glasgow prognostic score
• Neutrophil to lymphocyte ratio
• Non-small cell lung cancer
• Overall survival
• Wild-type epidermal growth factor receptor

• Epidermal growth factor receptor mutation
• Epidermal growth factor receptor tyrosine kinase inhibitors
• Lymphocyte-to-monocyte ratio
• Neutrophil-to-lymphocyte ratio
• Non-small cell lung cancer
• Overall survival
• Progression-free survival
• Retrospective analysis

Numerous studies have reported the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in malignancies, but its prognostic value among lung cancer remains controversial. This meta-analysis aimed to explore the prognostic significance of LMR in lung cancer patients.

Eight studies including 3954 patients were included in this meta-analysis. Pooled results indicated that low LMR was significantly associated with poorer progression-free survival (hazard ratio (HR): 1.431, 95% confidence interval (CI): 1.294–1.582, p < 0.001) and overall survival (OS) (HR: 1.651, 95% CI: 1.306–2.086, p < 0.001), compared with high LMR. Similar results were observed in subgroups regardless of treatment, LMR cut-off value, or districts. However, no significant correlation between the LMR and OS was observed in the small cell lung cancer (SCLC) subgroup (HR = 1.262, 95% CI: 0.864–1.841, p = 0.229).

Identified literatures were extracted and retrieved from PubMed, Embase, Web of Science, and the Cochrane Library databases; All eligible studies focused on the association between LMR and the prognosis of lung cancer.

Low LMR is associated with poor outcomes among lung cancer patients. Further studies are needed to discuss the correlation between LMR and lung cancer prognosis.

• lung cancer
• lymphocyte to monocyte ratio (LMR)
• meta-analysis
• prognosis

• lymphocyte to monocyte ratio
• non-small cell lung cancer
• platelet count
• prognosis

The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

• epithelial ovarian cancer
• lymphocyte-to-monocyteratio
• neoadjuvant chemotherapy
• prognosis

To determine if the lymphocyte-to-monocyte ratio (LMR) could be helpful in predicting survival in patients with pancreatic adenocarcinoma.

We retrospectively reviewed the medical records of all patients diagnosed with pancreatic adenocarcinoma in the VA North Texas Healthcare System from January 2005 to December 2010. The LMR was calculated from peripheral blood cell counts obtained at the time of diagnosis of pancreatic cancer by dividing the absolute lymphocyte count by the absolute monocyte count. A Univariable Cox regression analysis was performed using these data, and hazard ratios (HR) and 95%CI were calculated. The median LMR (2.05) was used to dichotomize patients into high-LMR and low-LMR groups and the log rank test was used to compare survival between the two groups.

We identified 97 patients with pancreatic adenocarcinoma (all men, 66% white, 30% African-American). The mean age and weight at diagnosis were 66.0 ± 0.9 (SEM) years and 80.4 ± 1.7 kg respectively. Mean absolute lymphocyte and monocyte values were 1.50 ± 0.07 K/μL and 0.74 ± 0.03 K/μL respectively. Mean, median and range of LMR was 2.36, 2.05 and 0.4-12 respectively. In the univariable Cox regression analysis, we found that an increased LMR was a significant indicator of improved overall survival in patients with pancreatic adenocarcinoma (HR = 0.83; 95%CI: 0.70-0.98; P = 0.027). Kaplan-Meier analysis revealed an overall median survival of 128 d (95%CI: 80-162 d). The median survival of patients in the high-LMR (> 2.05) group was significantly greater than the low-LMR group (≤ 2.05) (194 d vs 93 d; P = 0.03), validating a significant survival advantage in patients with a high LMR.

The LMR at diagnosis is a significant predictor for survival and can provide useful prognostic information in the management of patients with pancreatic adenocarcinoma.

• Prognosis
• Lymphocyte-to-monocyte ratio
• Pancreatic adenocarcinoma
• Mortality
• Biomarker

To was to determine the impact of chronic obstructive pulmonary disease (COPD) and active smoking on the efficacy of chemotherapy and complete blood count (CBC) in patients with non-small cell lung cancer (NSCLC).

The retrospective evaluation included 50 patients with stage IIIB–IV NSCLC, who started cisplatin-based chemotherapy. Peripheral blood CBC values were collected for testing before chemotherapy and after the first and third cycles.

COPD was diagnosed in 49% of patients, while 42% of those enrolled were current smokers. Current smoking (p = 0.92) and COPD (p = 0.91) status did not affect the response to treatment. The non-COPD population presented a significantly higher pretreatment absolute lymphocyte count (ALC) than the COPD population (2.31 vs. 1.81 × 10⁹/l; p = 0.0374). Also, only the non-COPD group demonstrated an elevated absolute monocyte count (AMC) following the first and third cycles of chemotherapy (p = 0.004). In current smokers, pretreatment values for white blood cells (WBC), absolute neutrophil count (ANC), and platelets (PLT) were higher than in the ex-smoker population (WBC 9.94 vs. 8.7 (× 10⁹/l); p = 0.01; ANC 6.47 vs. 5.61 (× 10⁹/l); p = 0.037; PLT 316 vs. 266 (× 10⁹/l); p = 0.049). Ex-smokers demonstrated AMC level elevation after the first cycle of chemotherapy and PLT level elevation after the third cycle, while current smokers also demonstrated an early decrease in LMR.

COPD and smoking induce chronic systemic inflammation and oxidative stress, which influence the results of standard laboratory tests, but do not change the response rate of lung cancer on chemotherapy.

• chemotherapy
• chronic obstructive pulmonary disease
• non-small cell lung cancer
• smoking

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0–2: 11.2 months, PS 3–4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

• Bone Neoplasms/secondary
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/pathology
• ErbB Receptors/genetics
• Female
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Male
• Middle Aged
• Survival Analysis

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil‐lymphocyte ratio (NLR), the platelet‐lymphocyte ratio (PLR), and the lymphocyte‐monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease‐specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C‐index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1–2 vs. T3–4), N stage (N0–1 vs. N2–3) and pretreatment GPS (0 vs. 1–2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008, <0.001, 0.004, 0.018, and 0.004, respectively). A nomogram was established by involving all the factors above. Its C‐index for predicting the DSS of the validation set was 0.734 (standard error 0.056). Pretreatment GPS, NLR, and LMR were independent prognostic factors of NPC. The nomogram based on them could be used to predict the DSS of NPC patients.

• Disease-specific survival
• inflammatory biomarkers
• nasopharyngeal carcinoma
• nomogram
• prediction

The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio.

Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were characterised by microarray. Transcript expression was tested for association with ML ratio calculated from leucocyte differential counts by linear regression.

The ML ratio was associated with mycobacterial growth in vitro (β = 2.23, SE 0.91, p = 0.02). Using sorted monocytes and lymphocytes, in vivo ML ratio (% variance explained R² = 11%, p = 0.02) dominated over in vitro ratios (R² = 5%, p = 0.10) in explaining mycobacterial growth. Expression of 906 genes was associated with the ML ratio and 53 with monocyte count alone. ML-ratio associated genes were enriched for type-I and -II interferon signalling (p = 1.2 × 10^− 8), and for genes under transcriptional control of IRF1, IRF2, RUNX1, RELA and ESRRB. The ML-ratio-associated gene set was enriched in TB disease (3.11-fold, 95% CI: 2.28–4.19, p = 5.7 × 10^− 12) and other inflammatory diseases including atopy, HIV, IBD and SLE.

The ML ratio is associated with distinct transcriptional and anti-mycobacterial profiles of monocytes that may explain the disease associations of the ML ratio.

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A pathophysiological basis for involvement of the ML ratio in infectious, malignant and cardiovascular diseases is unclear.

Enumeration of the absolute count of white blood cell subsets is one of the most frequently performed tests in clinical practice. Recently, elevation in the monocytes:lymphocytes (ML) ratio was linked to increased risk of tuberculosis and malaria disease, and poorer outcomes for many cancers and cardiovascular diseases. We sought to understand the mechanism of these disease associations. We found that the ML ratio reflects the functional capacity of monocytes and that genes that are differentially expressed in monocytes from donors with a high ML ratio are similar to those in other diseases such as HIV and inflammatory bowel disease. Because a specific type of blood-making stem cell regulates the ML ratio, it is plausible that the ratio reflects monocyte function because it is a clue to different monocyte origins. Our findings offer a mechanism for the predictive value of the ML ratio that may help improve its clinical utility.

Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC.

This retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan–Meier and multivariate Cox regression methods.

The 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P<0.001), ΔNLR (P=0.004), and change in LMR (ΔLMR) (P=0.025) were significant predictors of DFS and that age (P=0.039), smoking status (P=0.042), postoperative NLR (P<0.001), ΔNLR (P=0.004), and ΔLMR (P=0.011) were independent predictors of OS. Multivariate analysis confirmed that postoperative NLR (hazard ratio [HR] =2.435, P=0.001) and ΔNLR (HR =2.103, P=0.012) were independent predictors of DFS and that postoperative NLR (HR =2.747, P=0.001) and ΔNLR (HR =2.052, P=0.018) were significant prognostic factors of OS.

Our study reported for the first time that postoperative NLR and ΔNLR – but not preoperative NLR – were independent prognostic factors of DFS and OS in patients with stage I NSCLC who underwent complete resection. This easily available biomarker might be helpful in individual risk assessment.

• neutrophil-to-lymphocyte ratio
• non-small-cell lung cancer
• prognosis
• stage I
• surgery

Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this. While it is relatively easy to measure general signs of immune suppression, it turns out that accurate monitoring of the frequency and function of immune-suppressive cells is still difficult. A lack of truly specific markers, the phenotypic complexity among suppressive cells of the same lineage, but potentially with different functions and functional assays that may not cover every mechanistic aspect of immune suppression are among the reasons complicating proper assessments. Technical innovations in flow and mass cytometry will allow for more complete sets of markers to precisely determine phenotype and associated function. There is, however, a clear need for functional assays that recapitulate more of the mechanisms employed to suppress the immune system.

• anti-tumor response
• functional assays
• immune dysfunction
• immunomonitoring
• immunosuppression
• myeloid-derived suppressor cells
• phenotyping
• regulatory T cells
• tumor-associated macrophages
• tumor-associated neutrophils

• Lymphocyte to monocyte ratio
• non-small cell lung cancer
• prognosis

This retrospective study aimed to investigate the prognostic significance of pretreatment lymphocyte-to-monocyte ratio (LMR) in locally advanced cervical cancer and its effect on overall survival.

The usual blood routine test was quantitatively performed to detect LMR. Signal strengths of human papilloma virus (HPV) type DNA in detected cervical cancer samples using hybrid capture 2 were analyzed in relative light units (RLU) compared with 1 pg/mL of HPV type 16 DNA-positive control (RLU/PC) samples. A total of 1.0 RLU/PC (~1 pg/mL) was used as the threshold for a positive result. The HPV-positive specimens were typed using reverse-hybridization line probe assay.

The LMR and HPV DNA were found to be independent prognostic markers for 5-year overall survival (OS) and progression-free survival, respectively. Their joint detection may further enhance the predictive value for OS. In the positive HR (high risk)-HPV DNA status subgroup, LMR had a positive effect on improved OS but not in the non-HR HPV DNA status subgroup.

The LMR and HR-HPV DNA status can be identified as independent prognostic factors. The different influences of LMR in combined chemoradiotherapy on survival may be related to HR-HPV DNA status. The combined detection of LMR and HR-HPV DNA status may contribute to screening prognosis.

• Cervical carcinoma
• Human papilloma virus
• Hybrid capture 2
• Lymphocyte to monocyte ratio
• Prognosis

• cancer
• inflammation
• lymphocyte to monocyte ratio
• meta-analysis
• prognosis

• Disease Progression
• Disease-Free Survival
• Humans
• Inflammation/immunology
• Inflammation/mortality
• Inflammation/pathology
• Inflammation/therapy
• Lymphocytes/immunology
• Monocytes/immunology
• Neoplasms/immunology
• Neoplasms/mortality
• Neoplasms/pathology
• Neoplasms/therapy
• Odds Ratio
• Predictive Value of Tests
• Risk Factors
• Time Factors
• Treatment Outcome

• Endometrial Cancer
• Lymphocytes
• Monocytes