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

• Published in: BMC cancer 2024-07, Vol.24 (1), p.869-14, Article 869
• Main Authors: Yang, Jiayi, Ding, Xinyi, Fang, Zhang, Wu, Shaoxian, Yuan, Maoling, Chen, Rongzhang, Xu, Qinlan, Gao, Xinran, Wu, Haoyu, Chen, Lujun, Zheng, Xiao, Jiang, Jingting
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Biomarkers; Cancer therapies; CD8 antigen; CD8+T cells; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell interactions; Cells; Colon cancer; Colonic Neoplasms - immunology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal carcinoma; Correlation analysis; Female; Gene expression; Genetic engineering; Granzyme A; Granzymes - metabolism; GSDMB; Humans; Immune checkpoint; Immunogenicity; Immunohistochemistry; Immunotherapy; Interferon-gamma - metabolism; Interferon-γ; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical prognosis; Metastases; Metastasis; Patients; Pyroptosis; Single-Cell Analysis; Software; Spatial distribution; Survival analysis; Transforming growth factor-b; Tumor cells; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor-infiltrating lymphocytes; γ-Interferon
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-12605-y

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