• CT
• hepatocellular carcinoma
• inflammatory biomarkers
• pathological grade
• radiomics

• CD20 + cell
• CD3 + cell
• Colorectal cancer
• Prognosis
• Schistosomiasis
• Tumor-infiltrating lymphocytes

• Artificial Intelligence
• CD8-Positive T-Lymphocytes
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/pathology
• Humans
• Lymphocyte Count
• Lymphocytes, Tumor-Infiltrating/pathology

• CD3
• CD8
• FoxP3
• colon cancer
• colorectal carcinoma
• digital image analysis
• immunohistochemistry
• immunoscore
• rectal cancer
• survival
• tumour infiltrating lymphocytes

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2^−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.

• Colorectal cancer
• DNA mismatch repair
• Genomic instability
• Lynch syndrome
• Microsatellite instability
• Prognosis
• Sporadic cancer
• Survival

Recent studies in non-colorectal malignancy have associated T resident memory (T_RM) cells with improved patient survival. It is unknown if T_RM plays a role in colorectal cancer (CRC).

To examine the potential role of T_RM cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status.

Patients with known MSI and BRAF mutation status were eligible for inclusion in this study. CRC tumour sections stained with haematoxylin and eosin were microscopically reviewed and the images scanned prior to assessment for location of invading edge and core of tumour. Sequential sections were prepared for quantitative multiplex immunohistochemistry (IHC) staining. Opal Multiplex IHC staining was performed with appropriate positive and negative controls and imaged using a standard fluorescent microscope fitted with a spectral scanning camera (Mantra) in conjunction with Mantra snap software. Images were unmixed and annotated in inForm 2.2.0. Statistical analysis was performed using Graphpad Prism Version 7 and Stata Version 15.

Seventy-two patients with known MSI and BRAF status were included in the study. All patients were assessed for MSI by IHC and high resolution capillary electrophoresis testing and 44 of these patients successfully underwent quantitative multiplex IHC staining. Overall, there was a statistically significant increase in CD8+ T_RM cells in the MSI (BRAF mutant and wild type) group over the microsatellite stable (MSS) group. There was a statistically significant difference in CD8+ T_RM between high level MSI (MSI-H):BRAF mutant [22.57, 95% confidence interval (CI): 14.31-30.84] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0076 andMSI-H:BRAF wild type [16.18 (95%CI: 10.44-21.93)] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0279. There was no statistically significant difference in CD8 T cells (both CD8+CD103- and CD8+CD103+T_RM) between MSI-H: BRAF mutant and wild type CRC.

This study has shown that CD8+ T_RM are found in greater abundance in MSI-H CRC, both BRAF mutant and MSI-H:BRAF wild type, when compared with their MSS counterpart. CD8+ T_RM may play a role in the immunogenicity in MSI-H CRC (BRAF mutant and BRAF wild type). Further studies should focus on the potential immunogenic qualities of T_RM cells and investigate potential immunotherapeutic approaches to improve treatment and survival associated with CRC.

• Tissue resident memory cells
• Resident memory T cells
• Colorectal cancer
• Microsatellite instability
• BRAF
• DNA mismatch repair
• Immunotherapy
• Prognosis

• CD4+ T cells
• immunotherapy
• tumor

• SFB 1399 & EXC 2180 Deutsche Forschungsgemeinschaft

• MAMs
• T cells
• TAMs
• bone metastasis
• efferocytosis
• immunosuppression
• immunotherapy
• macrophage polarization

• 241295 Consejo Nacional de Ciencia y Tecnología
• P01-CA093900 NIH HHS

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the Isoflux^TM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively.

• circulating tumour cells
• colorectal cancer
• colorectal surgery
• microsatellite instability

• Aged
• Aged, 80 and over
• Carcinoembryonic Antigen/blood
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Female
• Humans
• Male
• Microsatellite Instability
• Middle Aged
• Neoplasm Staging
• Neoplastic Cells, Circulating/metabolism
• Poisson Distribution
• Postoperative Period
• Preoperative Period
• Statistics, Nonparametric

Colorectal cancer (CRC) is a leading cause of death among cancer patients. This heterogeneous disease is characterized by alterations in multiple molecular pathways throughout its development. Mutations in RAS, along with the mismatch repair gene deficiency, are currently routinely tested in clinics. Such biomarkers provide information for patient risk stratification and for the choice of the best treatment options. Nevertheless, reliable and powerful prognostic markers that can identify “high-risk” CRC patients, who might benefit from adjuvant chemotherapy, in early stages, are currently missing. To bridge this gap, genomic information has increasingly gained interest as a potential method for determining the risk of recurrence. However, due to several limitations of gene-based signatures, these have not yet been clinically implemented. In this review, we describe the different molecular markers in clinical use for CRC, highlight new markers that might become indispensable over the next years, discuss recently developed gene expression-based tests and highlight the challenges in biomarker research.

• biomarkers
• challenges
• clinical test
• clinical transition
• colorectal cancer
• early stage CRC
• gene signature
• molecular markers

• Ethnicity
• Hepatocellular carcinoma
• Neutrophil-to-lymphocyte ratio
• Prognosis
• Socioeconomic status

• Adenocarcinoma
• CRP
• Lymphocyte
• Neutrophil
• Pancreas

The aim of the study was to evaluate a prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) on long-term survival of cirrhotic and noncirrhotic hepatocellular cancer (HCC) patients managed by a curative-intent liver surgery in a developing country.

During the study period between November 1, 2001, and December 31, 2012, 109 patients underwent potentially curative hepatectomy for HCC. Data were retrospectively reviewed from the prospectively collected database. The median follow-up was 25 months. NLR was estimated by dividing an absolute neutrophil count by an absolute lymphocyte count from the differential blood count. Receiver operating characteristic curve was constructed to assess the ability of NLR to predict long-term outcomes and to determine an optimal cutoff value for all patients group, the subgroup with cirrhosis, and the subgroup without cirrhosis. The optimal cutoff values were 1.28, 1.28, and 2.09, respectively.

The overall 3- and 5-year survival rates were 49% and 45%, respectively, for low NLR group and 38% and 26%, respectively, for high NLR group. The difference was statistically significant (p=0.015). Overall survival was similar between low and high NLR groups in patients with cirrhosis; no difference was found between the groups (p=0.124). In patients without cirrhosis, low NLR group had longer overall survival compared with high NLR group (p=0.015). Univariate analysis identified four factors as significant predictors of long-term survival: cirrhosis, Child-Pugh score, platelet count, and NLR. On multivariate analysis, only platelet count and NLR were independent prognostic factors of long-term survival.

Prognostic value of NLR was confirmed in noncirrhotic HCC patients who underwent curative-intent liver surgery. In HCC patients with cirrhosis, the prognostic role of NLR was not confirmed.

• cirrhosis
• hepatocellular carcinoma
• inflammation
• liver resection
• neutrophil-to-lymphocyte ratio

• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms/pathology
• Colonic Neoplasms/surgery
• Female
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local/pathology
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Sigmoid Neoplasms/pathology
• Sigmoid Neoplasms/surgery

• colorectal cancer
• metastatic status
• stage IV
• survival
• tumor-infiltrating lymphocytes

During their development and progression tumors acquire numerous mutations that, when translated into proteins give rise to neoantigens that can be recognized by T cells. Initially, neoantigens were not recognized as preferred targets for cancer immunotherapy due to their enormous diversity and the therefore limited options to develop “one fits all” pharmacologic solutions. In recent years, the experience obtained in clinical trials demonstrating a predictive role of neoantigens in checkpoint inhibition has changed our view on the clinical potential of neoantigens in cancer immunotherapy. Technological advances such as sequencing of whole cancer genomes, the development of reliable algorithms for epitope prediction, and an increasing number of immunotherapeutic options now facilitate the development of personalized tumor therapies directly targeting a patient’s neoantigenic burden. Preclinical studies in mice that support the excellent therapeutic potential of neoantigen-directed immunotherapies have provided blueprints on how this methodology can be translated into clinical applications in humans. Consistently, very recent clinical studies on personalized vaccinations targeting in silico predicted neoepitopes shed a first light on the therapeutic potential of personalized, neoantigen-directed immunotherapies. In our review, we discuss the various subtypes of tumor antigens with a focus on neoantigens and their potential in cancer immunotherapy. We will describe the current methods and techniques of detection as well as the structural requirements for neoantigens that are needed for their recognition by T cells and for tumor destruction. To assess the clinical potential of neoantigens, we will discuss their occurrence and functional relevance in spontaneous and hereditary cancers and their prognostic and predictive value. We will present in detail the existing immunotherapeutic options that exploit the neoantigen burden of tumors encompassing both preclinical efforts that provided convincing technological proof-of-concept and the current clinical studies confirming the potential of neoantigen-directed immunotherapies.

• adoptive transfer
• mutations
• neoantigens
• personalized cancer immunotherapy
• vaccination

T lymphocytes exert important homeostatic functions in the healthy intestinal mucosa, whereas in case of colorectal cancer (CRC), infiltration of T lymphocytes into the tumor is crucial for an effective anti-tumor immune response. In both situations, the recruitment mechanisms of T lymphocytes into the tissues are essential for the immunological functions deciding the outcome. The recruitment of T lymphocytes is largely dependent on their expression of various chemokine receptors. The aim of this study was to identify potential chemokine receptors involved in the recruitment of T lymphocytes to normal human colonic mucosa and to CRC tissue, respectively, by examining the expression of 16 different chemokine receptors on T lymphocytes isolated from these tissues.

Tissues were collected from patients undergoing bowel resection for CRC. Lymphocytes were isolated through enzymatic tissue degradation of CRC tissue and nearby located unaffected mucosa, respectively. The expression of a broad panel of chemokine receptors on the freshly isolated T lymphocytes was examined by flow cytometry.

In the normal colonic mucosa, the frequencies of cells expressing CCR2, CCR4, CXCR3, and CXCR6 differed significantly between CD4⁺ and CD8⁺ T lymphocytes, suggesting that the molecular mechanisms mediating T lymphocyte recruitment to the gut differ between CD4⁺ and CD8⁺ T lymphocytes. In CRC, the frequencies of cells expressing CCR2 and CXCR5 were significantly lower in both the CD4⁺ and CD8⁺ T lymphocyte populations compared to unaffected colonic mucosa, and the frequency of CCR9⁺ cytotoxic T lymphocytes was significantly decreased in CRC tissue.

With regard to the normal gut mucosa, the results suggest that the molecular mechanisms mediating T lymphocyte recruitment differ between CD4⁺ and CD8⁺ T lymphocytes, which are important for understanding gut homeostasis. Importantly, T lymphocytes from CRC compared to normal colonic tissue displayed a distinct chemokine receptor expression profile, suggesting that mechanisms for recruitment of T lymphocytes to CRC tissue are skewed compared to normal colonic mucosa. Understanding these mechanisms could help in developing new strategies in cancer immunotherapy and to optimize already available alternatives such as immune checkpoint inhibitors.

• Chemokine receptor
• Colorectal cancer
• Homing
• Mucosa
• T lymphocyte

• Colon cancer
• lymph node yield
• population studies
• survival factors

The aim of this study was to investigate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) correlated with some tissue molecules as predictive markers for recurrence in colon cancer.

A total of 30 patients diagnosed with colon cancer stage II or III who underwent optimal surgery were enrolled in study. Tumor markers CEA and CA 19-9 were determined before surgery. Tumor samples were prepared using tissue microarray kit (TMA) then stained for different cellular markers (Ki 67, HER2, BCL2, CD56, CD4, CD8) and analyzed using Inforatio programme for quantitative determination. All patients received standard adjuvant treatment, which consisted of eight cycles chemotherapy type XELOX. The patients were followed up for 3 years.

Upon 3 years follow-up, 67% of patients developed tumor relapse, the most common site of metastasis being the liver. No correlations were observed between either serum or tissue tumor markers and the risk of tumor relapse.

Over 50% of patients with colon cancer who had optimal treatment developed metastasis. No statistically significant predictive value for investigated molecules was found. Future studies are needed to confirm the use of molecular markers in monitoring patients with colorectal cancer

• chemotherapy
• colon cancer
• predictive markers

• Microsatellite instability
• Nivolumab
• PD-L1
• Pembrolizumab
• TILs

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular/diagnosis
• Disease-Free Survival
• Female
• Fibrosis/metabolism
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/diagnosis
• Lymphatic Metastasis
• Lymphocytes/pathology
• Male
• Middle Aged
• Neutrophils/metabolism
• Plasma Cells/pathology
• Prognosis
• Proportional Hazards Models
• Recurrence
• Retrospective Studies
• Young Adult

• T cells
• colorectal cancer
• immune response
• lymphocyte
• tumor microenvironment

• Colorectal cancer prognosis
• Histopathological characteristics
• Immunohistochemical characteristics
• MTHFR C677T polymorphism

• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/pathology
• Genotype
• Humans
• Immunohistochemistry
• Lymphocytes, Tumor-Infiltrating/pathology
• Methylenetetrahydrofolate Reductase (NADPH2)/genetics
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Prognosis
• Retrospective Studies

Giving strong prognostic information, T‐cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T‐bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype‐high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild‐type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1‐attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T‐bet may be a valuable marker in the clinical setting. Our results also indicate that T‐bet is of value when analysed in molecular subgroups of CRC, allowing identification of patients with especially poor prognosis who are in need of extended treatment.

• BRAF
• KRAS
• Th1 lymphocytes
• colorectal cancer
• intratumoural subsites
• molecular subgroups
• prognosis

• Colorectal cancer
• FOXP3+ Tregs
• immunoscore
• prognosis

• Aged
• Biomarkers, Tumor/analysis
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Female
• Forkhead Transcription Factors/analysis
• Germany
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymphocyte Count
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/pathology
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Staging
• Predictive Value of Tests
• Proportional Hazards Models
• Switzerland
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/pathology
• Time Factors
• Treatment Outcome

• 5-fluorouracil
• arterial cisplatin
• hepatic arterial infusion chemotherapy
• neutrophil/lymphocyte ratio

• tumor microenvironment
• tumor stroma
• tumor heterogeneity
• rnaseq
• omic analysis
• intravital imaging
• deep-tissue imaging
• tissue clearing
• personalized therapy

• Animals
• Cell Communication/genetics
• Cell Communication/physiology
• Computational Biology
• Diagnostic Imaging
• Humans
• Microscopy
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/physiopathology
• Stromal Cells/pathology
• Stromal Cells/physiology
• Tumor Microenvironment/genetics
• Tumor Microenvironment/physiology

• K99 CA158066 NCI NIH HHS
• R00 CA158066 NCI NIH HHS
• R01 CA194697 NCI NIH HHS
• CA158066-04 NCI NIH HHS

To find improved tools for prognostic evaluation in patients with colorectal cancer (CRC), we have analysed how infiltration of cytotoxic T lymphocytes (CD8⁺) and regulatory T lymphocytes (FoxP3⁺) correlates to prognosis, not only according to quantity and relation, but also to subsite within tumours of different molecular characteristics (microsatellite instability and CpG island methylator phenotype status).

CD8 and FOXP3 expression was evaluated by immunohistochemistry in 426 archival tumour tissue samples from patients surgically resected for CRC. The average infiltration of CD8⁺ and FOXP3⁺ cells was assessed along the tumour invasive front, in the tumour centre and within the tumour epithelium (intraepithelial).

We found that infiltration of CD8⁺ T lymphocytes within the tumour epithelium provided the strongest prognostic information (P<0.001). At the tumour invasive front and tumour centre, FOXP3 expression withheld the strongest association to prognosis (P<0.001), suggesting FOXP3⁺ T-lymphocyte infiltration to be a better prognostic tool than CD8⁺ T lymphocytes at these intratumoural subsites. We further analysed the possible prognostic impact of the relation between these T-cell subsets, finding that a high intraepithelial CD8 expression was associated with a better patient outcome, independent of FOXP3 infiltration. In groups of low intraepithelial CD8 expression, however, a high infiltration rate of FOXP3⁺ cells at the tumour invasive front, significantly improved prognosis.

Analyses of intraepithelial infiltration of CD8⁺ T lymphocytes, infiltration of FOXP3⁺ T lymphocytes at the tumour front or centre, and the relation between these subsets, may be a valuable tool for predicting prognosis in colon cancer.

Neutrophil-lymphocyte ratio (NLR) has recently been reported as a predictor of Hepatocellular carcinoma (HCC). However, its prognostic value in HCC still remains controversial. In this study, we aimed to evaluate the association between NLR and clinical outcome of HCC patients by performing meta-analysis.

A comprehensive literature search for relevant studies published up to August 2013 was performed by using PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures.

A total of 15 studies encompassing 3094 patients were included in this meta-analysis. Our pooled results showed that high NLR was associated with poor overall survival (OS) and disease free survival (DFS) in HCC initially treated by liver transplantation (HR = 3.42, 95% CI:2.41-4.85,P = 0.000; HR = 5.90, 95% CI:3.99-8.70,P = 0.000, respectively) and surgical resection (HR = 3.33, 95% CI:2.23-4.98, P = 0.000; HR = 2.10, 95% CI: 2.06–2.14, respectively). High NLR was also associated with poor OS in HCC treated by radiofrequency-ablation (HR = 1.28, 95%CI: 1.10-1.48, P = 0.000), TACE (HR = 2.52, 95% CI: 1.64-3.86, P = 0.000) and mixed treatment (HR = 1.85, 95%  CI: 1.40-2.44, P = 0.000), respectively. In addition, high NLR was significantly correlated with the presence of vascular invasion (OR = 2.69, 95% CI: 2.01–3.59, P = 0.000), tumor multifocality (OR = 1.74, 95% CI: 1.30–2.34, P = 0.000) and higher incidence of AFP ≥ 400 ng/ml (OR = 1.46, 95% CI: 1.01–2.09, P = 0.04).

Elevated NLR indicates a poor prognosis for patients with HCC. NLR may be a convenient, easily-obtained, low cost and reliable biomarker with prognostic potential for HCC.

• B cell
• T cell
• meningioma
• tumor-infiltrating lymphocytes

Until now, the anatomic extent of tumor (TNM classification) has been by far the most important factor to predict the prognosis of colorectal cancer patients. However, in recent years, data collected from large cohorts of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients’ disease-free and overall survival. Tumoral and immunological markers predicted by systems biology methods are involved in the shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches. Global analysis of tumor microenvironment showed that the nature, the functional orientation, the density, and the location of adaptive immune cells within distinct tumor regions influence the risk of relapse events. The density and the immune cell location within the tumor have a prognostic value that is superior to the TNM classification, and tumor invasion is statistically dependent on the host-immune reaction. Thus, the strength of the immune reaction could advance our understanding of cancer evolution and have important consequences in clinical practice.

• Animals
• Humans
• Neoplasm Staging
• Neoplasms/immunology
• Neoplasms/pathology
• Neoplasms/therapy
• Prognosis
• T-Lymphocytes/immunology
• Tumor Microenvironment