Clinical significance of CD161 + CD8 + T cells in the tumor microenvironment of esophageal squamous cell carcinoma and their association with the 4-1BB signaling pathway

Background CD161 + CD8 + T cells, a cytotoxic T cell subset, remain poorly defined in terms of their clinical significance and functional role in esophageal squamous cell carcinoma (ESCC), which has limited the advancement of precision immunotherapy strategies. Methods We integrated a multicenter cohort of ESCC patients who underwent either surgery or neoadjuvant therapy (chemotherapy or chemoimmunotherapy). Multiplex immunofluorescence staining, survival analyses, and assessment of major pathological response (MPR) and pathological complete response (pCR) were performed to elucidate the clinical relevance of CD161 + CD8 + T cell infiltration. The functional state and cellular interactions of this subset were characterized using single-cell RNA sequencing. A CT-based radiomics model was also developed for non-invasive prediction. Results High intratumoral infiltration of CD161 + CD8 + T cells was identified as an independent prognostic factor for prolonged overall survival and disease-free survival (both p