Detection of virus in colorectal cancer and the tumor immune microenvironment in EBV-associated colorectal cancer

Background: The role played by oncogenic viruses in colorectal cancer is currently a topic of widespread interest. This study focused on the prevalence of viruses’ infection in colorectal cancer and its association with tumor immune microenvironment. Methods A total of 82 colorectal cancer samples were collected from January 2017 to January 2019. Tissue DNA was extracted and the infection rate of Epstein-Barr virus, human papillomavirus (HPV), cytomegalovirus (CMV) and human polyomavirus 2 (JCV) in colorectal cancer were detected by the methods of PCR or nested PCR. The differences in the expression of immune microenvironment-related proteins in EBV-associated colorectal cancer (EBVaCRC) and EBV-negative colorectal cancer (EBVnCRC) were analyzed by immunohistochemistry. Clinical characteristics of patients with EBV-associated colorectal cancer were analyzed by by chi-square test and non-parametric test. Results Epstein-Barr virus (EBV) demonstrated the highest prevalence (18.3%), whereas human papillomavirus (HPV), cytomegalovirus (CMV), and JC virus (JCV) were not detected. The expression of immune markers CD3, CD8, CD20, CD56, CD68 and FOXP3 was significantly higher in EBVaCRC than EBVnCRC, while CTLA4 and CD163 expression was not significantly different between the two groups. Moreover, the expression levels of PD-1 and PD-L1, as assessed by IRS scores, were significantly elevated in EBVaCRC compared to EBVnCRC. There were no significant differences in gender, age, tumor size and metastasis, tumor type, and prognosis between EBVaCRC and EBVnCRC patients, except for clinical stage, which was significantly lower in the former. Conclusion EBV had the highest detection rate among the common oncogenic viruses of colorectal cancer tested in this study. EBVaCRC has an inflammatory immune microenvironment consisting of increased immune cell infiltration and upregulation of immune checkpoints, and is a candidate for immune checkpoint therapy.