CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer

Peng, Qi-Hua; Wang, Chunhua; Chen, Hongmin; Zhang, Rongxin; Pan, Zhizhong; Zhang, Lu; Wang, Gaoyuan; Yue, Xin; Huang, Wenlin; Liu, Ranyi

doi:10.1136/jitc-2020-001638

Cited by 51 publications

(45 citation statements)

References 44 publications

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“…They also found that CMTM6 levels are positively correlated with the immune response in CRC cells [32]. Similarly, we found that the expression of PD-L1 in TC and IC were positively correlated with CMTM6 in CRC.…”

Section: Pd-l1supporting

confidence: 80%

The predictive value and correlation of β-catenin, CMTM6, and PD-L1 expression in colorectal cancer

Qiu

et al. 2022

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CMTM6, and PD-L1 immunohistochemical expression in is CRC still unknown and need to be further verified. We evaluated t -catenin, CMTM6, PD-L1, and MMR (mismatch repair) proteins by immunohistochemistry in CRC tissue microarray (TMA), and -catenin, CMTM6, PD-L1 expression, MMR status, and clinicopathological features in 704 CRC patients. Positive expression of PD-L1 in tumor cells (TC) is associated with more frequent dMMR (mismatch repair deficient) status, CMTM6 expression, right colon, and younger CRC patients. The expression of PD-L1 in tumor-infiltrating immune cells -catenin, and CMTM6 expression. In univariate analysis, age, histological subtype, histologic grade, lymphatic metastasis, TNM stage, MMR status, and expression of PD-L1 protein in IC were significantly associated with the overall survival. In multivariate analysis, age, histologic grade, TNM stage, MMR status, and expression of PD-L1 protein in IC were independent prognostic factors. The overall survival of the adjuvant chemotherapy group was significantly higher than those non-chemotherapy in TNM stage III-IV CRC patients, but no significant overall survival improvement was found in the positive PD-L1 in TC, positive PD--catenin expression, or dMMR status subgroups. Expression of CMTM6 and PD--catenin and reliable biomarkers for the prediction of responding to chemotherapy. The expression of -catenin/CMTM6/PD-L1 and MMR status may be valuable biomarkers for guiding different treatment strategies in CRC patients.

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Section: Pd-l1supporting

confidence: 80%

The predictive value and correlation of β-catenin, CMTM6, and PD-L1 expression in colorectal cancer

Qiu

et al. 2022

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“…Conlon, liver, lung cancers are the common malignancies in most countries, and immune cells infiltration into tumour tissue and immune cells exhaustion lead to a poor prognosis [ 1 – 4 ]. The infiltration number and exhaustion state of immune cells could exert a key role in cancer progression, and immune combination therapy is becoming a promising strategy for enhancing traditional chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

DFNA5 regulates immune cells infiltration and exhaustion

Pei

Jiang

et al. 2022

Cancer Cell Int

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Background DFNA5 (GSDME) belongs to Gasdermin familily that is involved in a variety of cancers and triggers cell pyroptosis after chemical treatment. However, the relationship in DFNA5 between prognosis and immune cells in diverse cancers has been receiving little attention. Tumor immune cells infiltration and exhaustion may associate with patients prognosis. The roles of DFNA5 in tumor immune cells infiltration and exhaustion have not been clarified. Methods The expression level of DFNA5 was determined by the Tumour Immune Estimation Resource and the Oncomine database. Then the impacts of DFNA5 in prognosis were assessed by Kaplan–Meier plotter and ULACAN. The correlations between DFNA5 and tumour-infiltrating lymphocytes were explored by TIMER. In addition, the relationships in the expression levels of DFNA5 and typical genes combination of tumour-infiltrating lymphocytes were analysed by GEPIA and TIMER. In this study, we screened the chemokine and immune related proteins interacted with DFNA5 using TurboID system to explore the instantaneous or weak interactions. Results DFNA5 significantly influences the prognosis in different cancers according to The Cancer Genome Atlas (TCGA). The expression levels of DFNA5 showed positive correlations to the infiltration of macrophages, CD8 + T cells, CD4 + T cells in liver hepatocellular carcinoma (LIHC), colon adenocarcinoma (COAD), and lung adenocarcinoma (LUAD). DFNA5 expression displayed obvious correlations with multiple lymphocytes gene makers in COAD, LIHC and LUAD. DFNA5 expression has effects on the prognosis of liver hepatocellular carcinoma and LUAD. DFNA5 upregulated the expression levels of PDCD1 and CD274 in a dose-dependent manner. Chemokine and immune related proteins interact with DFNA5. Conclusions These results indicate that DFNA5 is related to patient prognosis and immune cells, consisting of macrophages, CD4 + T cells, and CD8 + T cells, in diverse cancers. In addition, DFNA5 expression might contribute to the regulation of T cell exhaustion, tumour-associated macrophages (TAMs), and Tregs in COAD, LIHC and LUAD. DFNA5 may regulate immune infiltration via EIF2AK2. IFNGR1 was related to the functions of PD-L1 expression and PD-1 checkpoint pathway. These results indicate that DFNA5 levels may be act as a prognostic factor and predict the degrees of immune cells infiltration in LIHC and LUAD.

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“…The levels of CMTM6 mRNA and protein were both applied for the prognosis analysis of different types of tumor and contradictory conclusions were obtained. At the mRNA level, a high level of CMTM6 is correlated with better survival in gastric cancer, colorectal cancer [20,29], while high level of CMTM6 is correlated with worse survival in gliomas [16]. At the protein level evaluated by immunohistochemistry, highly expressed CMTM6 indicates poor prognosis in gastric cancer, HNSCC, hepatocellular carcinoma [21,[30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Co-Expression with Membrane CMTM6/4 on Tumor Epithelium Enhances the Prediction Value of PD-L1 on Anti-PD-1/L1 Therapeutic Efficacy in Gastric Adenocarcinoma

Wang

Peng

Liu

et al. 2021

Cancers

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Anti-PD-1/L1 immunotherapy has been intensively used in heavily treated population with advanced gastric adenocarcinoma. However, the immunotherapeutic efficacy is low even in PD-L1 positive patients. We aimed to establish a new strategy based on the co-expression of CMTM6/4 and PD-L1 for patient stratification before immunotherapy. By analyzing the data obtained from TCGA and single-cell RNA sequencing at the mRNA level, and 6-color multiplex immunofluorescence staining of tumor tissues in tissue array and 48-case pre-immunotherapy patients at the protein level, we found that CMTM6/4 and PD-L1 co-expressed in both epithelial and mesenchymal regions of gastric adenocarcinoma. The tumor tissues had higher levels of CMTM6/4 expression than their adjacent ones. A positive correlation was found between the expression of CMTM6/4 and the expression of PD-L1 in tumor epithelium. Epithelial co-expression of CMTM6/4 and PD-L1 in gastric tumor region was associated with shorter overall survival but better short-term response to anti-PD-1/L1 immunotherapy. Thus, we developed a predictive model and three pathological patterns based on the membrane co-expression of CMTM6/4 and PD-L1 in tumor epithelial cells for pre-immunotherapy patient screening in gastric adenocarcinoma.

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CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer

Cited by 51 publications

References 44 publications

The predictive value and correlation of β-catenin, CMTM6, and PD-L1 expression in colorectal cancer

The predictive value and correlation of β-catenin, CMTM6, and PD-L1 expression in colorectal cancer

DFNA5 regulates immune cells infiltration and exhaustion

Co-Expression with Membrane CMTM6/4 on Tumor Epithelium Enhances the Prediction Value of PD-L1 on Anti-PD-1/L1 Therapeutic Efficacy in Gastric Adenocarcinoma

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