Description
Colorectal cancer (CRC) is the third leading cause of cancer death in developed countries. In the United States, the incidence and mortality of CRC among African Americans are greater than in Caucasians. One possible explanation for these disparities could be underlying genetic differences in the immune response among the different races. CD8+ T cells infiltrating tumor epithelium have been shown to correlate with better prognosis. A recent study done by our lab indicated that CD8+ cell infiltration does not significantly differ by race but the function of these cells was not evaluated. Granzyme B (GzmB) is a serine protease secreted by cytotoxic T cells and natural killer cells which is able to induce apoptosis of harmful target cells in a perforin-dependent manner. Therefore, evaluating GzmB expression levels is informative as to the cytotoxic function of the immune cells in the tumor. The primary goal of this study is to measure the GzmB expression in CRC with regard to the evident racial disparity. The secondary goal of this study is to correlate GzmB expression with CD8+ cell and CD57+ cell densities among CRC samples. Formalin-fixed paraffin-embedded archival colon cancer tissue slides were obtained from the North Carolina Colon Cancer Study, a population-based cohort (45% blacks, 55% whites). Immunohistochemistry was used to detect the presence of GzmB and the mean number of both tumor epithelial-infiltrating and total intratumoral-infiltrating GzmB cells per patient was quantified from the 3 highest GzmB infiltration fields (200X magnification) in a blind study. 244 patient tumor samples were stained (115 blacks, 129 whites) and statistically analyzed. We found a significant difference in GzmB+ cells between African American and Caucasian CRC patient tumors (p<0.05). No significant difference in gender was found, indicating the difference in race is not due to gender. Significant correlations were found between GzmB+ and CD8+ cells (p<0.0001) as well as GzmB+ and CD57+ cells (p<0.0001). These studies demonstrate differences in immune responses may contribute to racial disparities in CRC.
