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Updated: Aug 31, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
Shengkui Tan1,2, Xuefeng Guo1, Chunhua Bei1
1Department of Epidemiology and Statistics, School of Public Health, Guilin Medical University, Guilin, 541199, China.
Background:
Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC).
Methods:
The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307.
Results:
Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy.
Conclusions:
CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.
Insights
Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) and programmed cell death ligand 1 (PD-L1) co-expression, along with T cell infiltration, significantly impacts hepatocellular carcinoma (HCC) patient prognosis. This highlights the importance of considering combined protein effects in HCC treatment strategies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) maintains programmed cell death ligand 1 (PD-L1) expression, potentially influencing tumor immunity.
- The specific role of CMTM4 in hepatocellular carcinoma (HCC) immunity remains unclear, despite its suggested role in tumor progression and immunotherapy.
Purpose of the Study:
- To investigate the role of CMTM4 in HCC immunity and its prognostic significance.
- To explore the relationship between CMTM4, PD-L1, and T cell infiltration in HCC patients.
Main Methods:
- Immunohistochemistry (IHC) was used to detect CMTM4, PD-L1, CD4, and CD8 protein expression in 90 HCC tissues.
- mRNA expression and prognosis data were analyzed from The Cancer Genome Atlas (TCGA-LIHC).
- Immune therapy cohorts (Imvigor210, GSE176307) were utilized for validation.
Main Results:
- Single protein expression of CMTM4, PD-L1, CD4, or CD8 did not significantly correlate with HCC patient prognosis.
- High co-expression of CMTM4, PD-L1, and CD4 was associated with a good prognosis in HCC patients.
- CMTM4 expression positively correlated with CD4+ and CD8+ T cell infiltration, and high CMTM4/PD-L1 expression with CD4+ T cell infiltration predicted better overall survival.
Conclusions:
- CMTM4 and PD-L1 co-expression, in conjunction with T cell infiltration, holds prognostic significance in HCC.
- Combined therapeutic strategies considering multiple protein interactions are recommended for HCC treatment.
