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

Abstract

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.

Inference of immune cell composition on the expression profiles of mouse tissue

“…Based on their cell surface markers, immune cell types could be qualitatively and quantitatively measured via several experimental methods, including flow cytometry7, affinity purification8, and immunohistochemistry9. Using flow cytometry, Gunn et al .…”

“…developed a protocol that could accurately quantify 11 immune cell types in non-lymphoid tissues7. McGuire et al 9. used immunohistochemistry to assess the differences in the number of intraepithelial CD8+ T cells between African Americans and Caucasians.…”

Racial Disparity in Gastrointestinal Cancer Risk

“…Histological evaluation of Black CRCs as compared to NHW CRCs demonstrate: (a) an absence of high levels of CD8 + T cell counts in MSI tumors [81] and (b) lower infiltration of immune cells expressing granzyme B, a cytotoxic marker, particularly at the invasive borders of the tumor [99]. These observations of reduced immune function against cancer cells contribute to the aggressiveness of the tumor.…”

Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin?

“…The number of granzyme B secreting cytotoxic cells has been reported to be significantly lower in African American patients compared to Caucasians, suggesting that the functional activity of inflammatory cells is not identical across races [76]. Two other studies analyzed the response of cultured monocytes and macrophages to bacterial [71] and viral infections [72] in individuals of African and European ancestry.…”