Immune Checkpoints And Inflammation In Colon Tumors From African Americans

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. Recent findings suggest that this may be related to the differential expression in genes linked to inflammation and immune response. Therefore, we aimed to investigate if tumors from AA colon cancer patients diverge in their immunologic profile from CA and if the immune response of a CRC cell line derived from an AA tumor will differ from a CA CRC cell line. Additionally, we are recording the genetic profiles of colon tumors and outcomes from AA patients at our institution. Methods: Using DESeq2 we evaluated the differential gene expression pattern by whole transcriptome sequencing (Illumina) of 10 CRC tissues (and matching adjacent non-tumor tissue) from both AA and CA individuals. We focused on genes involved in immune checkpoints and inflammation. We also examined the secretion of Interleukin 8 (IL-8) in plasma from our AA CRC patients. For the in vitro experiments, we used the AA tumor-derived colon cancer cell line SB-521, generated in Dr. Williams9 laboratory, and the CA colon cancer cell line HT-29 to determine if the cell lines expressed the Programmed death-ligand 1 (PD-L1). Lastly, we analyzed the microsatellite (MSI) status and MMR mutations in tumors from AA colon cancer patients at our institution and correlated their genetic analysis to response to chemotherapies and survival. Results: The genomic data revealed that AA and CA tumors had a significant difference of expression in a total of 221 genes. Remarkably, some of these genes included PD1, IL1B, IL17A, IL10, IL5, CD80 and FOXP3. The cytokine IL-8 concentration detected by ELISA in plasma of these patients revealed a differential expression between early stages (I, II) and late stages (III, IV). As hypothesized, the MSI and AA tumor-derived cell line SB-521 expressed PD-L1 and showed an increase in protein levels in response to TNF-α treatment (the CA cell line HT-29 did not express PD-L1). Lastly, our retrospective data (N=200 patients) demonstrated that up to 20% of our AA colon cancer patients have MSI and/or MMR mutations. Conclusions: Altogether, our results suggest that the immune profiles of the tumors from AA patients differ from CA and these differences could be used as biomarkers and to guide therapeutic strategy for these populations. Also, since the AA cell line presented distinct inflammatory patterns and when compared to the HT-29 CA cell line, it is a potential model to study MSI and PD-L1 in AA. Hence, we aim to supplement our preliminary data on AA patients with MSI and MMR mutations at Downstate and to elucidate what other genomic differences exist and cytokines9 secretion patterns observed. In conclusion, we will address the immune and molecular biology of CRC tumors in AA through genomic and in vitro studies, and generate patient9s data on AA diagnosed with colon cancer. Citation Format: Jenny E. Paredes, Ping Ji, Maria Munoz-Sagastibelza, Sayed Imtiaz, Kaylene Barrera, Raavi Gupta, Maksim Agaronov, Henry Talus, Jovanny Zabaleta, Jennie Williams, Laura Martello-Rooney. Immune checkpoints and inflammation in colon tumors from African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 646.