Reshaping tumor immune microenvironment by Epstein-Barr virus activation in the stroma of colorectal cancer
Hyun Ju Park,
Eun Jeong Cho,
Ji-Hun Kim,
Sehun Lim,
Chang Ohk Sung
Affiliations
Hyun Ju Park
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Eun Jeong Cho
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Ji-Hun Kim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
Sehun Lim
Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Republic of Korea; Corresponding author
Chang Ohk Sung
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea; Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Corresponding author
Summary: 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.
