JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment

• Published in: In vitro cellular & developmental biology. Animal Vol. 60; no. 4; pp. 382 - 396
• Main Authors: Cheng, Shiliang, Li, Meng, Li, Chunguang, Dai, Yonggang, Zhuo, Jinhua, Wang, Jue, Qian, Jingrong, Hao, Zhihao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2024; Society for In Vitro Biology
• Subjects: Adenocarcinoma; Agonists; Animal Genetics and Genomics; Animal models; Animals; Apoptosis; Apoptosis - drug effects; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Bioinformatics; Biomarkers; Biomedical and Life Sciences; Cancer; Carcinogenesis; Carcinogenesis - drug effects; Carcinogenesis - genetics; Carcinogenesis - immunology; Carcinogens; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Developmental Biology; Flow cytometry; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immune checkpoint; Immunoassay; Immunomodulation; Immunotherapy; Inflammation; Inhibitors; Life Sciences; Lymphocytes; Lymphocytes T; Male; Mice; Neoplasms; Nucleotide sequence; Overexpression; PD-1 protein; PD-L1 protein; Placebo effect; Polymerase chain reaction; Proliferation; Stem Cells; Targeted cancer therapy; Toxicity; Tumor cells; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; Colon adenocarcinoma; CXADR; Immune checkpoints; Tumor microenvironment; JAML
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-024-00881-8

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8 + T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers. The AOM/DSS mouse model of colorectal cancer was constructed. The expression levels of JAML, CXADR and PD-1 were detected by PCR and Western blot, and the proportion of CD8 + T cells and exhausted T cells were detected by flow cytometry. The expression levels of JAML and CXADR were significantly decreased in colon cancer tissues. Overexpression of JAML can promote the proliferation of T cells, secrete a variety of inflammatory factors. Overexpression of CXADR can reduce the proliferation of colorectal cancer cells, promote apoptosis, and down-regulate the migration and invasion ability of tumor cells. Both JAML agonists and PD-L1 inhibitors can effectively treat colorectal cancer, and the combined use of JAML agonists and PD-L1 inhibitors can enhance the effect. JAML can promote the proliferation and toxicity of CD8 + T cells and down-regulate the expression of immune checkpoints in colon cancer. CXADR can inhibit the proliferation of cancer cells and promote the apoptosis. JAML agonist can effectively treat colorectal cancer by regulating CD8 + T cells.