PLX170093

GSE146009: Immune-Related Gene Expression and Cytokine Secretion is Reduced Among African American Colon Cancer Patients

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could contribute to the disparities observed between these populations. Methods: We examined gene expression of 20 tumor and 20 non-tumor adjacent tissues from AA and the same number from CA by whole transcriptome sequencing and generated scores for immune cell populations by NanoString. In addition, we utilized The Cancer Genome Atlas (TCGA) database from AA (n = 55) and CA (n = 193) as a validation cohort. Finally, we measured the secretion of cytokines characteristic of effector T helper cell (Th) subsets by ELISA using plasma from each AA and CA participant. Results: Colon tumors from AA patients showed significant fold-change increase in gene expression when compared to CA for FOXP3 (6.97 vs. 3.15), IL1B (122 vs. 14) and IL8 (262 vs. 28) (p < 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and immunotherapy targets PDL1 (CD274) and CTLA4 (p < 0.05). TCGA data validated our observed higher expression of GZMB and PDL1 in CA patients as well as showed a 50% higher 5-year survival rate in AA patients with high expression of GZMB. Notably, our observations on immune cell populations show that AA tumors have significantly higher number of exhausted CD8+ cells (p < 0.01), mast cells (p < 0.02) and increased T regulatory cells when compared to CA. AA colon cancer patients differed from CA in cytokine production patterns in plasma (i.e. reduced IL-12). Conclusions: Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches. SOURCE: Jovanny Zabaleta (jzabal@lsuhsc.edu) - LCRC 909 Louisiana State University Health Sciences Center