ArticleDiscover oncology2025
Single-cell hdWGCNA identifies ICI-related-colitis key CD8 + T cells linked to immunotherapy response and prognosis in colon cancer.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn recent years, immune checkpoint inhibition therapy has brought hope for the treatment of malignancies. However, it can also lead to adverse reactions due to excessive immune activation, with checkpoint inhibitor-associated colitis (CIC) being one of them. This study aims to explore the immunological mechanisms in CIC and their impact on colon cancer prognosis and immune checkpoint therapy efficacy.
methodsSingle-cell RNA sequencing data from patients with PD-1 inhibitor-induced colitis and those without colitis were analysed to identify CIC-related CD8 + T cells through cell-cell communication and pseudotime analyses. High-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) was used to identify CIC-related gene modules. Additionally, the prognostic significance of key module gene expression in colon cancer was assessed, along with its impact on immune infiltration and immunotherapy response.
resultsCIC-key-CD8 T cells were significantly upregulated in PD1-induced colitis patients. These cells were in the early stages of CD8 + T cell development and exhibited a lack of normal function, including unique communication patterns via Galectin pathways. Increased presence of this immune cell population was correlated with worse clinical outcomes and limited immunotherapy efficacy in colon cancer. We developed a prognostic scoring model based on the expression patterns of four related genes (HSPA1B, HSPA1A, CRIP1, and TNFRSF25). Individuals identified as high-risk displayed elevated immune checkpoint expression levels and a more suppressive immune environment.
conclusionCIC-key-CD8 T cells are pivotal in modulating the tumour microenvironment and can significantly impact the clinical outcome of colon cancer. Their high infiltration rate correlates with poor outcomes and immunotherapy resistance. Targeting these cells may improve therapeutic strategies for cancer immune checkpoint inhibitor treatments.
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