S213 Intratumoral Human Cytomegalovirus Abundance in Colon Adenocarcinoma Is Associated With Poor Survival Outcomes and Increased Intratumoral Regulatory T-cell Infiltrate in Elderly Patients

Abstract

Introduction: Although higher rates of human cytomegalovirus (CMV) are known to be associated with colorectal cancer, the impact of CMV on patient survival and its impact on the immune milieu in the tumor microenvironment have not been studied extensively. As such, we assess the associations of intratumoral CMV RNA signatures in colon adenocarcinoma with overall and age-specific survival and intratumoral immune cell abundance. Methods: Microbial RNA sequencing (RNA-seq) data was procured as described previously by Poore et al. and used to calculate average log counts per million (CPM) of CMV. Abundance of intratumoral immune cell types was estimated via the quanTIseq method described previously by Finotello et al. The Cancer Genome Atlas Colon Adenocarcinoma clinical dataset was downloaded from cBioPortal.org. Only patients with primary tumor sites in the colon were included for further analysis. Survival data was processed using GraphPad Prism software to generate Kaplan-Meier curves. Relative hazard ratios (HRs) for overall and age-specific survival were estimated with cox proportional hazards models using the lifelines python package. Spearman correlation analysis was calculated with Bonferroni correction for multiple comparisons. Results: Our study included 432 patients with primary colon adenocarcinoma and CMV RNA-seq data. Comparison of the rate of overall survival for patients in the top and bottom quintiles of CMV log CPM showed higher CMV abundance was associated with significantly decreased survival (p=0.04) (Figure). When stratified by age, individuals aged ≥65 with higher CMV abundance had increased overall mortality risk (HR 1.21; p< 0.001) while no significant association was observed between CMV abundance and survival in those aged ≤55 (Table). Spearman correlation analysis showed intratumoral CMV signatures were significantly positively correlated with CD8+ T cell (correlation coefficient=0.20; p=0.001) and regulatory T cell (correlation coefficient=0.17; p=0.005) abundance in individuals aged ≥65 but not in those aged ≤55. Conclusion: To our knowledge, this is the largest study investigating associations of intratumoral CMV signatures with patient survival in colon adenocarcinoma and the first to characterize an age-specific correlation between intratumoral CMV and immune cell abundance. Further research elucidating the molecular mechanisms by which CMV modulates the tumor microenvironment is warranted.Figure 1.: Kaplan-Meier Overall Survival Curve comparing top quintile (n = 86, black) vs bottom quintile (n=86, gray) of CMV recoveries in Colon Adenocarcinoma Table 1. - Associations of intratumoral cytomegalovirus abundance, sex, and tumor stage with mortality risk in patients with colon adenocarcinoma stratified by age using Cox proportional hazards model Age ≥65 Parameter Hazard Ratio (HR) P-value CMV abundance Per unit increase in CMV log CPM 1.21 < 0.001 Sex Female 1 Male 1.04 0.94 Tumor stage I-II 1 III-IV 3.87 0.009 Age ≤55 CMV abundance Per unit increase in CMV log CPM 0.94 0.77 Sex Female 1 Male 0.94 0.91 Tumor stage I-II 1 III-IV 3.44 0.23