Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response

• Published in: Nature communications Vol. 12; no. 1; pp. 7297 - 14
• Main Authors: Yen, Yu-Ting, Chien, May, Wu, Pei-Yi, Ho, Chi-Chang, Ho, Chun-Te, Huang, Kevin Chih-Yang, Chiang, Shu-Fen, Chao, K. S. Clifford, Chen, William Tzu-Liang, Hung, Shih-Chieh
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 14; 14/19; 631/208/176/2016; 631/67/1504/1885/1393; 631/67/580/1884/2323; 692/4028/67/1059/2325; Acetylation; Animal models; Animals; Antigens - genetics; Antigens - immunology; Biomarkers; Breast cancer; Cancer; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Cytotoxicity; Deactivation; Deoxyribonucleic acid; DNA; DNA Methylation; DNA Mismatch Repair; DNA repair; E2F protein; Epigenetics; Gene expression; Gene silencing; Histone deacetylase; Histones; Humanities and Social Sciences; Humans; Immune Checkpoint Inhibitors - immunology; Immune response; Immune system; Inactivation; Infiltration; Lymphocytes; Lymphocytes T; Metastases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microsatellite Instability; Mismatch repair; MLH1 protein; multidisciplinary; Neoantigens; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - immunology; Phosphatase; Phosphoprotein phosphatase; Phosphorylation; Protein phosphatase; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - immunology; Proteins; Repair; Retina; Retinoblastoma; Retinoblastoma protein; Science; Science (multidisciplinary); T-Lymphocytes, Cytotoxic - immunology; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - immunology; Tumor cell lines; Tumors

Microsatellite-instable (MSI), a predictive biomarker for immune checkpoint blockade (ICB) response, is caused by mismatch repair deficiency (MMRd) that occurs through genetic or epigenetic silencing of MMR genes. Here, we report a mechanism of MMRd and demonstrate that protein phosphatase 2A (PP2A)...