Association of CD8+TILs co-expressing granzyme A and interferon-γ with colon cancer cells in the tumor microenvironment

作者：Jiayi Yang, Xinyi Ding, Fang Zhang, Shaoxian Wu, Maoling Yuan, Rongzhang Chen, Qinlan Xu, Xinran Gao, Haoyu Wu, Lujun Chen, Xiao Zheng, Jingting Jiang · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12605-y · 被引用次数：19 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Immune cells in cancer

Abstract CD8 + T cells secreting granzyme A (GZMA) can induce pyroptosis in tumor cells by effectively cleaving gasdermin B (GSDMB), which is stimulated by interferon-γ (IFN-γ). However, the interaction between GZMA-expressing CD8 + T cells and GSDMB-expressing tumor cells in colon cancer remains poorly understood. Our research employed multi-color immunohistochemistry (mIHC) staining and integrated clinical data to explore the spatial distribution and clinical relevance of GZMA- and IFN-γ-expressing CD8 + tumor-infiltrating lymphocytes (TILs), as well as GSDMB-expressing CK + cells, within the tumor microenvironment (TME) of human colon cancer samples. Additionally, we utilizing single-cell RNA sequencing (scRNA-seq) data to examine the functional dynamics and interactions among these cell populations. scRNA-seq analysis of colorectal cancer (CRC) tissues revealed that CD8 + TILs co-expressed GZMA and IFN-γ, but not other cell types. Our mIHC staining results indicated that a significant reduction in the infiltration of GZMA + IFN-γ + CD8 + TILs in colon cancer patients ( P < 0.01). Functional analysis results indicated that GZMA + IFN-γ + CD8 + TILs demonstrated enhanced activation and effector functions compared to other CD8 + TIL subsets. Furthermore, GSDMB-expressing CK + cells exhibited augmented immunogenicity. Correlation analysis highlighted a positive association between GSDMB + CK + cells and GZMA + IFN-γ + CD8 + TILs ( r = 0.221, P = 0.033). Analysis of cell-ce...