Influence of Race on Microsatellite Instability and CD8⁺ T Cell Infiltration in Colon Cancer

<div><p>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 (<i>P</i> = 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, <i>P</i><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.</p></div

CD8⁺ T cell infiltration in colon cancers.

<p>(A) CD8⁺ T cell counts between races, regardless of microsatellite instability. (B) CD8⁺ T cell counts between MSI and MSS cancers from African Americans. (C) CD8⁺ T cell counts between MSI and MSS cancers from Caucasians. The number above each dot blot are means; the horizontal bar represents the mean number among the cancers.</p

MSI vs. MSS clinicopathological associations between African Americans and Caucasians in the NCCCS.

<p>CA = Caucasian American; AA = African American. Lymphocytic pattern refers to infiltrate at the interface of the normal bowel wall and tumor. Crohn's-like pattern refers to lymphoid and granuloma-like clusters in the tumor, and intraepithelial lymphocytes.</p