CMTM6 and CMTM4 as two novel regulators of PD-L1 modulate the tumor microenvironment

Zhang, Tong; Yu, Haixiang; Dai, Xiangpeng

doi:10.3389/fimmu.2022.971428

Cited by 7 publications

(5 citation statements)

References 130 publications

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“…Evidence indicates that immune cells play an important role in tumor development, metastasis, and drug resistance [ 17 ]. We further explored the relationship between SERPINE1 and tumor immune cells.…”

Section: Resultsmentioning

confidence: 99%

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Guo

Sun

Chen

et al. 2023

Clin Exp Otorhinolaryngol

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Background: Nicotine is an ingredient of tobacco, and its exposure increases various cancer risks, including oral cancer. Previous studies have focused on its addictive properties, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process of nicotine promoting the occurrence and development of oral cancer through data mining and experimental verification. Methods: This study involved three parts. First, the key genes related to nicotine-related oral cancer were screened out through data mining; second, the expression and clinical significance of the key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results: SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways such as TNF and Apelin pathways; and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to Bleomycin and Docetaxel. Conclusion: This study revealed SERPINE1 as the key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

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Section: Resultsmentioning

confidence: 99%

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Guo

Sun

Chen

et al. 2023

Clin Exp Otorhinolaryngol

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“…CMTM6 functions as a novel regulator of PD-L1 expression by stabilizing the PD-L1 protein and inhibiting its ubiquitination. [ 9 , 18 ] Its high expression has been closely associated with the occurrence and progression of various cancers, including CRC. [ 19 ] The findings of this study indicate that high CMTM6 expression is a common molecular feature in patients with CRC and is closely correlated with the development of CRC.…”

Section: Discussionmentioning

confidence: 99%

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer

Lu,

Pan,

Yuan

et al. 2023

Medicine

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CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.

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“…As a result, tumour growth in KRAS-transformed cell xenografts was reduced by reducing SLC7A11 transformation and tumorigenicity and increasing glutathione synthesis [41,42]. Moreover, it has been revealed that the p53 gene may inhibit the development of cancer by triggering ferroptosis and limiting SLC7A11 expression [43,44].…”

Section: Interrelationship: Tme With the Development Of Ferroptosis I...mentioning

confidence: 99%

A review on comprehending immunotherapeutic approaches inducing ferroptosis: Managing tumour immunity

Chattopadhyay,

Hazra,

Mallick

et al. 2024

Immunology

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Ferroptosis, a necrotic, iron‐dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide‐loaded nano‐vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53‐SLC7A11‐GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy.

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CMTM6 and CMTM4 as two novel regulators of PD-L1 modulate the tumor microenvironment

Cited by 7 publications

References 130 publications

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer

A review on comprehending immunotherapeutic approaches inducing ferroptosis: Managing tumour immunity

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