Background: The aim of this study was to clarify the association between CMTM6 and PD-L1 expression as well as microenvironment in lung squamous carcinoma (LUSC).
Material And Methods: Using Spearman's correlation and Tumor Immune Estimation Resource (TIMER), we analyzed the relationship between CMTM6 and PD-L1 mRNA in LUSC. Immunohistochemistry (IHC) assay was applied to validate the correlation between CMTM6 and PD-L1 protein level in 80 LUSC samples originated from Shandong Provincial Hospital. Then, using The Cancer Genome Atlas (TCGA) database and fisher test, we analyzed the differential mutation genes in high and low CMTM6 expression group. TISIDB was used to explore the distribution of CMTM6 across immune- and molecular-subtypes. TCGA database and Gene Set variation analysis (GSVA) were used to analyze the relationship between CMTM6 and immune genes, immune related pathways.
Result: Positive correlation between CMTM6 and PD-L1 in mRNA and protein level was found in LUSC patients. More gene mutations were found in CMTM6 high expression group compared with low expression group. Meanwhile, we also found the correlation between CMTM6 expression and molecular subtypes, immune genes, immune related pathways. Furthermore, our result revealed that B cells memory, T cells memory testing, T cells folicular helper, macrophages M0, macrophages M1 and neutrophils varied significantly between patients with CMTM6 high and low expression group. Finally, we found that CMTM6 expression was positively related to CD8 + T cell, macrophage, neutrophil and dendtritic cell (all, P < 0.05) and negatively related to CD4 + T cell (P = 0.018).
Conclusion: CMTM6 is positively associated with PD-L1 expression and correlates with infiltration of immune cells in microenvironment of lung squamous carcinoma.
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http://dx.doi.org/10.1016/j.intimp.2020.106864 | DOI Listing |
Discov Oncol
December 2024
Department of Internal Medicine, Medical Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
We retrospectively analyzed 129 treatment-naïve head and neck squamous cell carcinomas (HNSCCs) for the expression of programmed death ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs). We evaluated the relationships among these markers, human papilloma virus (HPV) status, and overall survival (OS). PD-L1 and CMTM6 (combined positive score (CPS) ≥ 1 and ≥ 5) were detected in ~ 70% of HNSCCs.
View Article and Find Full Text PDFCancers (Basel)
September 2024
Instituto de Investigación en Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it has non-canonical subcellular localizations in cell lines derived from cervical cancer. Our objective was to determine whether CMTM6 is found in plasma derived from cervical cancer patients and its subcellular localization in cell lines.
View Article and Find Full Text PDFAsian J Surg
September 2024
Department of Transfusion, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. Electronic address:
Exp Mol Med
September 2024
Tumor Microenvironment and Metastasis, the Hormel Institute, University of Minnesota, Austin, MN, USA.
Liver metastasis of colorectal cancer (CRC) is a leading cause of death among cancer patients. The overexpression of glucose transporter 1 (Glut1) and enhanced glucose uptake that are associated with the Warburg effect are frequently observed in CRC liver metastases, but the underlying mechanisms remain poorly understood. CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) regulates the intracellular trafficking of programmed death-ligand-1 (PD-L1); therefore, we investigated whether CMTM6 regulates Glut1 trafficking and the Warburg effect in CRC cells.
View Article and Find Full Text PDFNat Commun
August 2024
Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, to confer lung cancer cell resistance to ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair of IR-induced DNA double-strand breaks (DSBs) and PD-L1 loss downregulates non-homologous end joining (NHEJ) while overexpression of PD-L1 upregulates NHEJ.
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