Decreased Anti-Tumor Cytotoxic Immunity among Microsatellite-Stable Colon Cancers from African Americans.

Colorectal cancer is a leading cause of cancer related deaths in the U.S., with African-Americans having higher incidence and mortality rates than Caucasian-Americans. Recent studies have demonstrated that anti-tumor cytotoxic T lymphocytes provide protection to patients with colon cancer while patients deficient in these responses have significantly worse prognosis. To determine if differences in cytotoxic immunity might play a role in racial disparities in colorectal cancer 258 microsatellite-stable colon tumors were examined for infiltrating immune biomarkers via immunohistochemistry. Descriptive summary statistics were calculated using two-sample Wilcoxon rank sum tests, while linear regression models with log-transformed data were used to assess differences in race and Pearson and Spearman correlations were used to correlate different biomarkers. The association between different biomarkers was also assessed using linear regression after adjusting for covariates. No significant differences were observed in CD8+ (p = 0.83), CD57+ (p = 0.55), and IL-17-expressing (p = 0.63) cell numbers within the tumor samples tested. When infiltration of granzyme B+ cells was analyzed, however, a significant difference was observed, with African Americans having lower infiltration of cells expressing this cytotoxic marker than Caucasians (p<0.01). Analysis of infiltrating granzyme B+ cells at the invasive borders of the tumor revealed an even greater difference by race (p<0.001). Taken together, the data presented suggest differences in anti-tumor immune cytotoxicity may be a contributing factor in the racial disparities observed in colorectal cancer.

Influence of race on microsatellite instability and CD8+ T cell infiltration in colon cancer.

African American patients with colorectal cancer show higher mortality than their Caucasian counterparts. Biology might play a partial role, and prior studies suggest a higher prevalence for microsatellite instability (MSI) among cancers from African Americans, albeit patients with MSI cancers have improved survival over patients with non-MSI cancers, counter to the outcome observed for African American patients. CD8+ T cell infiltration of colon cancer is postively correlated with MSI tumors, and is also related to improved outcome. Here, we utilized a 503-person, population-based colon cancer cohort comprising 45% African Americans to determine, under blinded conditions from all epidemiological data, the prevalence of MSI and associated CD8+ T cell infiltration within the cancers. Among Caucasian cancers, 14% were MSI, whereas African American cancers demonstrated 7% MSI (P = 0.009). Clinically, MSI cancers between races were similar; among microsatellite stable cancers, African American patients were younger, female, and with proximal cancers. CD8+ T cells were higher in MSI cancers (88.0 vs 30.4/hpf, P<0.0001), but was not different between races. Utilizing this population-based cohort, African American cancers show half the MSI prevalence of Caucasians without change in CD8+ T cell infiltration which may contribute towards their higher mortality from colon cancer.