Abstract C118: Tumor immune response in colon cancer African American patients and its role in cancer disparities

Abstract

Abstract Introduction: Colorectal cancer (CRC) is the third most common cancer among African Americans (AA) and when compared to Caucasian Americans (CA), they present more advanced CRC disease and lower survival rates. Our previous findings suggest that this may be related to the differential expression in genes linked to cell recruitment and immune response. Therefore, we aimed to investigate the cellular antitumor activity and mutational profile of colon tumors from AAs. We also examined the secretion of cytokines characteristic of immune responses by different effector T helper cells (Th) subsets in AA and CA patients, as well as cell lines, to see if these differences play a role in the health disparities observed between these populations. Lastly, we observed the expression of the Program Death Ligand 1 (PD-L1) in response to the cytokines IL-17A and TNF-α in a microsatellite-unstable (MSI) AA and a microsatellite-stable (MSS) CA colon cancer cell line. Methods: Using IHC, we evaluated the cell recruitment and activation of T and natural killer cells in AA tumors. For mutational analysis, we utilized the TruSight Tumor 170 RUO kit (Illumina). ELISA assays (RayBiotech) were used to examine the secretion of cytokines linked to Th subsets (Th1, Th2, Th17) and inflammation in plasma from the AA and CA CRC patients, as well as in supernatants from the AA and CA colon cancer cell lines. Western blots were used to observe the expression of PD-L1 in the in vitro models. Results: ELISAs of plasma of CA and AA patients revealed a differential Th cytokines production patterns between early-stages (I, II) and late-stage (III) disease. The MSI AA cell line showed an increase on PD-L1 protein expression in response to IL-17A and TNF-α with an additive effect when combined in equal concentrations. Lastly, the mutational sequencing allowed us to further investigate the potential alterations that are responsible for the differences that we observed in gene expression between AAs and CAs in our RNA and cytokine expression profiling. Conclusions: Our results indicate that the immune profiles of AA patients differ from CA in terms of cytokines' production; AAs expressed elevated IL-17A, whereas CA expressed elevated IFN-γ, the latter indicative of Th1 immunity that has a more favorable prognosis. As such, these differences could be used as biomarkers and to guide therapeutic strategy for these populations. The mutational sequencing will help us to elucidate the impaired tumor immune response in AAs with colon cancer when compared to CAs that we observed in terms of cell recruitment and cytokine secretion in our previous findings. Importantly, our data indicate that IL-17A and TNF-α promote the protein production of PD-L1 in an MSI AA cell line, which may result in the impairment of T cells' antitumor activity. Taken together, the differences in the immunologic profiles in AA when compared to CA suggest a deficiency of the appropriate immune defense mechanisms in this population that may contribute to the cancer health disparities among CRC patients. Citation Format: Jenny E. Paredes, Ping Ji, Jone Garai, Marzia Spagnardi, Maria Munoz-Sagastibelza, Sayed Imtiaz, Gayle Mendez, Mubarak Akadri, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Ellen Li, Jovanny Zabaleta, Laura Martello-Rooney, Jennie Williams. Tumor immune response in colon cancer African American patients and its role in cancer disparities [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C118.