English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 (T h ) 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.

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