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TNFRSF18+ Regulatory T Cells as a Potential Biomarker of Immunotherapeutic Outcomes in Immunosuppressed Colon Cancer
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DOI：10.1155/humu/5366828.png)
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Abstract
En 中文
Identifying reliable biomarkers to stratify colon cancer (CC) patients for immunotherapy remains a critical unmet clinical need due to the immunosuppressive nature of the tumor microenvironment. This study utilized TCGA-COAD transcriptomic data to classify patients into immunity-high and immunity-low phenotypes via single-sample GSEA, finding that the immunity-low subgroup exhibited significantly poorer survival (p = 0.038). Within this cohort, high expression of TNFRSF18 was identified as a key marker of inferior prognosis (p = 0.030). Single-cell RNA sequencing pinpointed TNFRSF18 expression primarily to Regulatory T cells (Tregs). Further validation in an independent immunotherapy cohort revealed that high infiltration of TNFRSF18+ Tregs significantly correlated with shorter disease-free and overall survival (p = 0.041 and p = 0.007). Functional ex vivo organoid experiments demonstrated that TNFRSF18-low tumors were susceptible to anti-PD-1 treatment, characterized by increased IFN-γ and GZMB secretion, whereas TNFRSF18-high tumors displayed therapeutic resistance. In conclusion, this study establishes TNFRSF18+ Tregs as a novel prognostic marker and a predictor of immunotherapy response in immunosuppressed CC, suggesting that targeting TNFRSF18 could potentially enhance the efficacy of anti-PD-1 therapies in resistant patient subsets.
Keywords:
colon cancer
immunosuppressive
organoid
TNFRSF18
Treg
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