The association between clinical outcome and CD8⁺ lymphocytic infiltration in advanced stages of colorectal cancer differs by latent virus infection in tumour tissue

Abstract

The association between clinical outcome and CD8 + lymphocytic infiltration in advanced stages of colorectal cancer differs by latent virus infection in tumour tissue Aims: In the near future, an immunoscore based on the quantification of lymphocytic populations can be expected as a fundamental supplement of colorectal cancer (CRC) classification. This study explored whether latent viral infection has an influence on prognostically relevant host immunity in CRC. Methods and results: CD8+ lymphocytic infiltration in three tumour compartments of 121 CRC was compared with clinical data and occurrence of latent infection with herpes simplex virus (HSV1, HSV2), cytomegalovirus (CMV), human papillomavirus (HPV16 and HPV18) in the tumour tissue, which was determined by polymerase chain reaction (PCR). Intraepithelial CD8 + lymphocytic infiltration (IE CD8+ ) showed a trend towards correlation with clinical stage (P = 0.073), significant differences between CRC with and without metastases (P = 0.001) and a significant correlation with overall survival (OS, P = 0.001). Each of these three clinical parameters showed a significant link to IE CD8+ in the virus DNAnegative (P-values: 0.001-0.036), but no significant differences in the virus DNA-positive subgroup, which is consistent with a moderating effect of virus DNA on these associations. A significant correlation of CD8 + infiltration in the invasive margin (IM CD8+ ) with OS (P = 0.016) was also moderated by virus DNA. Conclusion: Our data suggest a possible influence of latent viral infection on the association between clinical outcome and CD8 + lymphocytic infiltration in CRC tissue. After confirmation of these results by large cohort studies, a potential interaction between microbial pathogens and host immunity in CRC and its impact on prognostic immunoscores and/or new therapeutic strategies should be investigated further.