• HLA-G
• immune checkpoints
• immune evasion
• immune microenvironment
• urothelial cancer

• Humans
• HLA-G Antigens/immunology
• HLA-G Antigens/genetics
• Urinary Bladder Neoplasms/immunology
• Urinary Bladder Neoplasms/mortality
• Urinary Bladder Neoplasms/pathology
• Prognosis
• Tumor Microenvironment/immunology
• Female
• Male
• Aged
• Middle Aged
• Tumor Escape
• Biomarkers, Tumor
• Neoplasm Invasiveness
• Aged, 80 and over
• Immune Evasion

• Camrelizumab
• Case report
• Chemotherapy
• Pancreatic metastases
• Pulmonary sarcomatoid carcinoma

• Case report
• Chemotherapy
• Immunotherapy
• Jejunal sarcomatoid carcinoma
• Targeted therapy

• Adjuvant chemotherapy
• Aggressive pathology
• Lung cancer
• Prognosis
• Survival

• Humans
• Male
• Female
• Retrospective Studies
• Aged
• Lung Neoplasms/surgery
• Lung Neoplasms/pathology
• Lung Neoplasms/mortality
• Middle Aged
• Carcinoma, Non-Small-Cell Lung/surgery
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/mortality
• Neoplasm Staging
• Prognosis
• Japan/epidemiology
• Aged, 80 and over
• Adult
• Proportional Hazards Models
• Carcinosarcoma/surgery
• Carcinosarcoma/pathology
• Carcinosarcoma/mortality
• Chemotherapy, Adjuvant
• Pneumonectomy/methods

• Glycosylation
• Hyperprogressive disease
• Immune checkpoint inhibitor
• Interprotein interaction
• Tumor microenvironment

• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/drug therapy
• Liver Neoplasms/immunology
• Cell Proliferation/drug effects
• B7-H1 Antigen/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/immunology
• Mice
• Animals
• Cell Line, Tumor
• Signal Transduction
• Immune Checkpoint Inhibitors/pharmacology
• Immune Checkpoint Inhibitors/therapeutic use
• Receptor Protein-Tyrosine Kinases/immunology
• Antibodies, Monoclonal, Humanized/pharmacology
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antibodies, Monoclonal/pharmacology
• Antibodies, Monoclonal/therapeutic use
• Proto-Oncogene Proteins/metabolism
• Axl Receptor Tyrosine Kinase
• Xenograft Model Antitumor Assays

• 19K17507 Japan Society for the Promotion of Science

• APOBEC
• Exome sequencing
• MET
• Programmed cell death-ligand 1
• Pulmonary sarcomatoid carcinoma

• Humans
• Carcinoma, Non-Small-Cell Lung/pathology
• Lung Neoplasms/drug therapy
• B7-H1 Antigen/metabolism
• Kelch-Like ECH-Associated Protein 1/genetics
• Kelch-Like ECH-Associated Protein 1/metabolism
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• NF-E2-Related Factor 2/therapeutic use
• Mutation
• Genomics
• Carcinoma

• Pulmonary sarcomatoid carcinoma (PSC)
• biology
• clinical characteristics
• treatment strategies

• Immune checkpoint inhibitors
• Lung cancer
• Pulmonary sarcomatoid carcinoma
• Real-world data

• immunotherapy
• programmed death ligand 1
• sarcomatoid carcinoma
• tumor microenvironment
• undifferentiated carcinoma

• Female
• Humans
• B7-H1 Antigen/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Prognosis
• Rare Diseases/metabolism
• Carcinoma/metabolism
• Lung Neoplasms/pathology

• Genetic mutation
• MET exon 14
• Metastasis
• Protein kinase inhibitor
• sarcomatoid carcinoma

• brain metastasis
• non-squamous cell lung cancer
• pulmonary sarcomatous cancer
• rare lung cancer
• sarcomatoid variant

• anlotinib
• case report
• pembrolizumab
• pulmonary sarcomatoid carcinoma
• tumor mutation burden

• Female
• Humans
• Aged
• Carcinoma, Non-Small-Cell Lung/pathology
• Lung Neoplasms/pathology
• B7-H1 Antigen
• Quality of Life
• Antineoplastic Agents, Immunological/adverse effects
• Neoplasm Recurrence, Local/drug therapy
• Biomarkers, Tumor/genetics
• Carcinoma/drug therapy

• ONCOLOGY
• Sarcoma
• Thoracic medicine

• Humans
• Carcinoma
• Lung Neoplasms
• Nomograms
• Survival Analysis

• Fujian Provincial Finance Department
• Natural Science Foundation of Fujian Province

• Lung neoplasms
• Radiotherapy
• Sarcoma

• Computed tomography
• Non-small cell lung cancer
• Pulmonary sarcomatoid carcinoma

• Humans
• Carcinoma, Non-Small-Cell Lung/diagnostic imaging
• Carcinoma, Non-Small-Cell Lung/surgery
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/surgery
• Retrospective Studies
• Carcinoma
• Prognosis
• Tomography, X-Ray Computed

• the Ganzhou Science and Technology Planning Project
• National Natural Science Foundation of China
• Natural Science Foundation of Jiangxi Province
• Ganzhou Science and Technology Planning Project

• MET Exon 14 skipping mutations
• NSCLC
• PD-L1 expression
• PSC
• immunotherapy
• precision oncology
• processing escape
• pulmonary sarcomatoid carcinoma
• targeted therapy

• lung adenocarcinoma
• neoplasm of the lung

• Cytotoxic T-lymphocyte antigen 4
• Immunotherapy
• Programmed cell death ligand 1
• Renal pelvis
• Sarcomatoid
• Urothelial carcinoma

• Male
• Humans
• Aged
• Carcinoma, Transitional Cell/therapy
• Carcinoma, Transitional Cell/pathology
• Atrial Fibrillation/pathology
• Urinary Bladder Neoplasms/pathology
• Kidney Neoplasms/pathology
• Kidney Pelvis/pathology
• Carcinoma, Renal Cell/pathology
• Immunotherapy

• Hypoxia-inducible factor 1
• Hypoxic signaling pathways
• Non-small cell lung carcinoma
• Programmed death ligand-1

• camrelizumab
• case report
• obstructive atelectasis
• pulmonary sarcomatoid carcinoma
• tracheoscopic cryotherapy

• Beijing Science and Technology Planning Project

Previous studies have suggested that patients with pulmonary sarcomatoid carcinoma (PSC)may benefit from immune checkpoint inhibitors (ICIs); however, relevant data are lacking. This study aimed to establish the immunophenotype of PSC by assessing PD-L1 and CD8+ T-cell infiltration.

A retrospective analysis of pathologically confirmed PSC cases from two centers was performed from January 2009 to May 2021. According to the infiltration of CD8+ T cells in different spatial regions, patients were classified into three types: immune-inflamed, immune-excluded, and immune desert. PD-L1 staining was also performed on the intratumoral region and the tumor proportion score (TPS) was used for scoring. Combined with CD8+ T-cell infiltration and PD-L1 expression in the intratumoral region, immunophenotyping can be divided into four types: type I (PD-L1+/CD8+, adaptive immune resistance), type II (PD-L1-/CD8-, immunologic ignorance), type III (PD-L1+/CD8-, intrinsic induction), and type IV (PD-L1-/CD8+, tolerance). Finally, correlation analysis was performed on the immunophenotype, clinicopathological characteristics, and outcomes of the patients.

A total of 32 patients with PSC were included in the final analysis. Of these patients, 65.6% (21/32), 15.6% (5/32), and 18.8% (6/32) were classified as immune-inflamed, immune-excluded, and immune-desert, respectively. Notably, the immune-inflamed type is predominantly observed in pleomorphic carcinomas (PC, 66.7%). Moreover, among these participants, 19 (59.4%) were classified as PD-L1 positive according to the TPS score. In particular, 11 (34.4%) patients had PD-L1 TPS scores >50%. Next, we immunophenotyped patients with PSC based on CD8+ T cell infiltration and tumor cell PD-L1 expression (types I–IV). Type I (PD-L1+/CD8+, adaptive immune resistance) was the most prevalent subtype, accounting for 46.9% (15/32), followed by type II (PD-L1-/CD8-, immunological ignorance) (21.9%), type IV (PD-L1-/CD8+, tolerance) (18.7%), and type III (PD-L1+/CD8-, intrinsic induction) (12.5%). Finally, we performed a survival analysis and found that neither immunophenotype was a predictor of prognosis in patients with PSC. Multivariate analysis showed that pneumonectomy increased the risk of death by four times compared with lobectomy (RR: 4.1; 95% CI:1.3-12.4, P=0.014).

Patients with PSC are characterized by immune-inflamed type and type I (PD-L1+/CD8+, adaptive immune resistance), explaining the intrinsic reasons for their high response rate to immunotherapy.

• Humans
• B7-H1 Antigen/metabolism
• Lymphocytes, Tumor-Infiltrating
• Immunophenotyping
• Retrospective Studies
• Lung Neoplasms/pathology
• Carcinoma/metabolism

Renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation is a very dangerous malignant tumor and extremely rare in clinical practice. In general, these tumors with a dismal prognosis, and there is no standard treatment.

In this case, an 81-year-old male patient was diagnosed with right renal pelvic carcinoma. After an open right radical nephroureterectomy, postoperative pathological examination showed infiltrating urothelial carcinoma with sarcomatoid differentiation. Overexpression of programmed death ligand-1 by immunohistochemistry. The carcinoma recurred 4.5 months after surgery. After informed, tislelizumab combined with anlotinib were used as first-line treatment. The patients showed a clinical partial response that lasted for 20 months.

This case demonstrates the efficacy of tislelizumab combined with anlotinib in patients diagnosed with metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation. Moreover, to our knowledge, this is the first application of this treatment.

• Medical Science and Technology Project of Zhejiang Province
• Natural Science Foundation of Zhejiang Province
• Wu Jieping Medical Foundation

• non small cell lung cancer
• retrospective analysis
• sarcomatoid carcinoma

Lung cancer is the world leading cause of cancer death. Therefore, a better understanding of the disease is needed to improve patient survival. In this work, we have deleted the tumor suppressor genes Pten and Trp53 in adult mouse lungs to analyze its impact on tumor formation. Double mutant mice develop Adenocarcinoma and Pulmonary Sarcomatoid Carcinoma, two different types of Non-Small Cell Carcinoma whose biological relationships are a matter of debate. The former is very common, with various models described and some therapeutic options. The latter is very rare with very poor prognosis, no effective treatment and lack of models reported so far. Interestingly, this study reports the first mouse model of pulmonary sarcomatoid carcinoma available for preclinical research.

Lung cancer remains the leading cause of cancer deaths worldwide. Among the Non-Small Cell Carcinoma (NSCLC) category, Adenocarcinoma (ADC) represents the most common type, with different reported driver mutations, a bunch of models described and therapeutic options. Meanwhile, Pulmonary Sarcomatoid Carcinoma (PSC) is one of the rarest, with very poor outcomes, scarce availability of patient material, no effective therapies and no models available for preclinical research. Here, we describe that the combined deletion of Pten and Trp53 in the lungs of adult conditional mice leads to the development of both ADC and PSC irrespective of the lung targeted cell type after naphthalene induced airway epithelial regeneration. Although this model shows long latency periods and incomplete penetrance for tumor development, it is the first PSC mouse model reported so far, and sheds light on the relationships between ADC and PSC and their cells of origin. Moreover, human ADC show strong transcriptomic similarities to the mouse PSC, providing a link between both tumor types and the human ADC.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen “albumin paclitaxel + cisplatin,” but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 10⁵ IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

• National Natural Science Foundation of China
• Natural Science Foundation of Jiangsu Province

With significant advances in the diagnostic tools and treatment modalities of cancer, the incidence of multiple primary malignancies (MPMs) has increased in the last decades. The therapeutic option changed with the arising of immune checkpoint inhibitors (ICIs), which have improved the survival of a broad spectrum of tumors. However, little information is available when it comes to the efficacy, resistance, and underlying mechanisms of ICIs.

A 67-year-old woman was diagnosed with pulmonary sarcomatoid carcinoma (PSC) with a history of hepatocellular carcinoma (HCC) and viral hepatitis B. Following the lack of response to systemic chemotherapy, she was treated with camrelizumab, an anti-programmed cell death protein 1 monoclonal antibody, in combination with chemotherapy, and a partial response was obtained both in PSC and HCC. After a course of 9-month treatment, the PSC lesion shrank still, while HCC was evaluated as a progressive disease with an increase in the diameter of liver neoplasm, elevated alpha-fetoprotein, and enlarged abdominal lymph nodes. Then, with the addition of radiotherapy for abdominal metastasis, the lung lesion was continuously shrinking. In the meantime, the liver neoplasm and abdominal lymph nodes showed no significant enlargement.

Camrelizumab combination therapy could consistently benefit the MPM patients with PSC and HCC, which may be a promising option for patients with MPMs.

Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. A 43-year-old female patient presenting with a lung mass with multiple brain metastases, carcinomatous pericarditis, and multiple bone metastases was referred to our department. Transbronchial biopsy confirmed the diagnosis of PPC harboring an EGFR mutation with exon 19 deletion. Subsequently, she was treated with osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, which resulted in partial response with shrinkage of the primary lesion and brain metastases. This partial response remained durable for 11 months with an ongoing regimen. The current case suggests that osimertinib would show promising effects as a first-line treatment for PPCs harboring EGFR mutations, as well as a reasonable sequence of therapy followed by immune checkpoint inhibitor-based regimens.

Pulmonary sarcomatoid carcinoma (PSC) is an unconventional non-small-cell lung cancer (NSCLC) that is currently managed under guidelines used for conventional NSCLC and has poor survival. Surgery is the optimal choice for resectable PSC, and the prevalence of mutations in this type of tumor laid the foundation for novel systemic therapies such as targeted therapy and immunotherapy. PSC is resistant to chemotherapy and radiotherapy, and the effects of the 2 therapies are controversial. Targeted therapies have been reported to confer survival benefits, and savolitinib, an oral selective MET tyrosine-kinase inhibitor, has been approved in metastatic patients with MET exon 14 skipping mutations. Expression and positive rate of programmed death ligand 1 in PSC are high; our previous research has also revealed a high mutational burden and a T-cell-inflamed microenvironment of PSC. Correspondingly, immune checkpoint inhibitors have shown preliminary antitumor effects (overall response rates of 40.5% (15/37) and 31.6% (6/19) in two retrospective studies, respectively) in PSC patients. In summary, patients should receive operations at an early stage and multimodality treatments are needed to maximize the benefits of patients with advanced disease.

Sarcomatoid carcinoma (SC) is a rare lung cancer subtype with poor prognosis and lack of effective treatment regimens. Studies concerning SC indicated common programmed death ligand-1 (PD-L1) overexpression and higher tumor mutational burden, leading to potential benefits from immunotherapy. The present case is the first report employing PD-L1 inhibitor durvalumab following definitive concurrent chemoradiotherapy (cCRT) in a patient with mediastinal lymph node metastatic SC, which was considered as a high probability of pulmonary origin but unclear primary lesion. After the 19-month follow-up, there was neither local recurrence nor distant metastasis. The patient was in a good condition, with the thoracic lesion controlled at Partial response-Response Evaluation Criteria in Solid Tumors (PR-RECIST). Except for grade 2 esophagitis, none of the other adverse events was observed. Our first attempt to adopt the consolidation immunotherapy after cCRT in unresectable locally advanced mediastinal SC exhibited improved local control, manageable safety, and potential survival benefits, representing a novel and promising therapeutic option for SC and encouraging further research exploration of this regimen in the future.

• PD-L1 inhibitors
• case report
• chemoradiotherapy
• immunotherapy
• sarcomatoid carcinoma

• immune checkpoint inhibitor
• malignant pulmonary methotelioma
• programed cell death ligand-1
• pulmonary sarcomatoid carcinoma

• Aged
• Aged, 80 and over
• B7-H1 Antigen/metabolism
• Biomarkers, Tumor/metabolism
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/metabolism
• Carcinoma, Non-Small-Cell Lung/pathology
• Female
• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Male
• Mesothelioma, Malignant/drug therapy
• Mesothelioma, Malignant/metabolism
• Mesothelioma, Malignant/pathology
• Middle Aged
• Pleural Neoplasms/drug therapy
• Pleural Neoplasms/metabolism
• Pleural Neoplasms/pathology
• Prognosis
• Retrospective Studies
• Thoracic Neoplasms/drug therapy
• Thoracic Neoplasms/metabolism
• Thoracic Neoplasms/pathology

• Biphasic tumour
• Epithelial-mesenchymal transition
• Non-small-cell lung cancer
• Sarcomatoid carcinoma
• Survival

Sarcomatoid carcinoma of the lung is an uncommon subtype of non-small-cell lung cancer (NSCLC). Even in the early stages, pulmonary sarcomatoid carcinoma (PSC) has a dismal prognosis when compared to other kinds of NSCLC with a mean survival of 9–12 months and a five-year survival rate of around 20%. We present the case of a 68-year-old woman with a two-month history of shortness of breath and cough. Initial computed tomography (CT) scan showed features of interstitial lung disease with chronic obstructive airway changes. After 34 months, the patient’s condition worsened with newer complaints of sore throat and hemoptysis. A repeat CT scan showed a ∼49x38x59mm size lesion in the superior segment of the left lower lobe. A core needle biopsy was performed, which revealed tumor cells consisting of irregular tubules and sarcomatoid components. The patient was started on chemotherapy. Unfortunately, she succumbed to her disease. Our case highlights the aggressiveness of PSC.

• Aged
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Female
• Humans
• Lung
• Lung Neoplasms
• Nepal

Pulmonary sarcomatoid carcinoma (PSC) is an uncommon subtype of lung cancer, and immune checkpoint blockade promises in clinical benefit. However, virtually nothing is known about the expression of common immune checkpoints in PSC. Here, we performed immunohistochemistry (IHC) to detect nine immune-related proteins in 97 PSC patients. Based on the univariable Cox regression, random forests were used to establish risk models for OS and DFS. Moreover, we used the GSEA, CIBERSORT, and ImmuCellAI to analyze the enriched pathways and microenvironment. Univariable analysis revealed that CD4 (P = 0.008), programmed cell death protein 1 (PD-1; P = 0.003), galectin-9 (Gal-9) on tumor cells (TCs; P = 0.021) were independent for DFS, while CD4 (P = 0.020), PD-1 (P = 0.004), Gal-9 (P = 0.033), and HLA on TILs (P = 0.031) were significant for OS. Meanwhile, the expression level of CD8 played a marginable role in DFS (P = 0.061), limited by the number of patients. The combination of Gal-9 on TC with CD4 and PD-1 on TILs demonstrated the most accurate prediction for DFS (AUC: 0.636-0.791, F1-score: 0.635–0.799), and a dramatic improvement to TNM-stage (P < 0.001 for F1-score of 1-y, 3-y, and 5-yDFS). A similar finding was also observed in the predictive ability of CD4 for OS (AUC: 0.602-0.678, F1-score: 0.635–0.679). CD4 was negatively associated with the infiltration of neutrophils (P = 0.015). PDCD1 (coding gene of PD-1) was positively correlated to the number of exhausted T cells (Texs; P = 0.020) and induced regulatory T cells (iTregs; P = 0.021), and LGALS9 (coding gene of Gal-9) was positively related to the level of dendritic cells (DCs; P = 0.021). Further, a higher combinational level of CD4, PDCD1 on TILs, and LAGLS9 on TCs were proved to be infiltrated with more M1-type macrophages (P < 0.05). We confirmed the expression status of nine immune-related proteins and established a TNM-Immune system for OS and DFS in PSC to assist clinical risk-stratification.

• Pulmonary sarcomatoid carcinoma
• immune checkpoint
• immunohistochemistry
• machine learning
• prognosis

A 52‐year‐old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death‐ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration.

• immune checkpoint inhibitor
• lung cancer
• pembrolizumab
• pseudoprogression
• spindle cell carcinoma

• ICIs
• Immunotherapy
• Lung cancer
• Rare histology
• Uncommon NSCLC

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Female
• Humans
• Immune Checkpoint Inhibitors/pharmacology
• Kaplan-Meier Estimate
• Lung Neoplasms/drug therapy
• Lung Neoplasms/pathology
• Male
• Middle Aged
• Proportional Hazards Models
• Retrospective Studies
• Survival Analysis

• histological variant
• immune checkpoint inhibitor
• pembrolizumab
• sarcomatoid
• urothelial cancer chemo-resistant