Differential Immune Signatures in the Tumor Microenvironment are Associated with Colorectal Cancer Racial Disparities: A Cohort Study of Biorepository Data

Abstract

Background: Disparities in colorectal cancer outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying colorectal cancer disparities, we compared the immunogenomic signatures of colorectal cancer from African American and European American patients.Methods: We identified all colorectal cancer patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed. Results: Of the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p=0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age and disease stage. Immunostimulatory and immunoinhibitory gene profiles including MHC expression differed by race. Conclusions: Differences in the tumor immune microenvironment of African American as compared to European American colorectal cancer specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.