Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients - PubMed

Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients - PubMed

Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients

Jenny Paredes 1, Jovanny Zabaleta 2 3, Jone Garai 3, Ping Ji 4, Sayed Imtiaz 5, Marzia Spagnardi 1, Joussette Alvarado 6, Li Li 3, Mubarak Akadri 1, Kaylene Barrera 5, Maria Munoz-Sagastibelza 1, Raavi Gupta 7, Mohamed Alshal 7, Maksim Agaronov 8, Henry Talus 9, Xuefeng Wang 10, John M Carethers 11, Jennie L Williams 4, Laura A Martello 1

Affiliations 

• PMID: 32983990
 
• PMCID: PMC7492388
 
• DOI: 10.3389/fonc.2020.01498

Free PMC article

Abstract

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 be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and 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 and CA 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 (6.22 vs. 3.22), IL1B (103 vs. 11.4) and IL8 (220 vs. 28.9) (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 the immunotherapy targets PDL1 (CD274) and CTLA4 (p < 0.05). TCGA data validated our observed higher gene expression of GZMB and PDL1 in CA patients when compared to AA. 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.

Keywords: African American; Nanostring; RNASeq; cancer disparities; colon cancer; cytokines.

Copyright © 2020 Paredes, Zabaleta, Garai, Ji, Imtiaz, Spagnardi, Alvarado, Li, Akadri, Barrera, Munoz-Sagastibelza, Gupta, Alshal, Agaronov, Talus, Wang, Carethers, Williams and Martello.