Reshaping tumor immune microenvironment by Epstein-Barr virus activation in the stroma of colorectal cancer

• Published in: iScience Vol. 26; no. 1; p. 105919
• Main Authors: Park, Hyun Ju, Cho, Eun Jeong, Kim, Ji-Hun, Lim, Sehun, Sung, Chang Ohk
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.01.2023; Elsevier
• Subjects: Cancer; Immunology; Microenvironment; Immunology; Microenvironment; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105919

The formation of tumor immune microenvironment (TIM) is complicated and poorly understood. Little is known about the effect of a viral infection potentially inducing an additional immune response in the TIM. Here, we identify Epstein-Barr virus (EBV) expression in the TIM in colorectal cancer (CRC) tissue through EBV-encoded RNA in-situ hybridization and RNA sequencing data and investigate the effects of EBV on TIM composition and clinical outcomes. EBV was detected in tumor-infiltrating lymphocytes, but not in cancer cells. EBV positivity was associated with older age, male sex, and SMAD4 mutations. EBV-positive tumors were characterized by enrichment in chemokine/cytokine signaling pathways and altered immune cell composition, including plasma and CD4 T cells, as well as cancer cells intrinsically enriched pathways related to immune tolerance, leading to poor prognosis. In conclusion, we identified EBV expression in TIM and suggested its association with poor prognosis by altering the TIM in CRC. [Display omitted] •EBV expression was identified in tumor stroma of CRC•CRC with the EBV-positive stroma has different immune composition and poor prognosis•Immune tolerance signaling in cancer cells against EBV are enriched Microenvironment; Immunology; Cancer.