Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct 1;78(19):5586-5599.
doi: 10.1158/0008-5472.CAN-17-3962. Epub 2018 Jul 16.

A RIPK3-PGE 2 Circuit Mediates Myeloid-Derived Suppressor Cell-Potentiated Colorectal Carcinogenesis

Affiliations
Free article

A RIPK3-PGE 2 Circuit Mediates Myeloid-Derived Suppressor Cell-Potentiated Colorectal Carcinogenesis

Guifang Yan et al. Cancer Res. .
Free article

Abstract

Receptor-interacting protein kinase 3 (RIPK3) is essential for mucosal repair in inflammatory bowel diseases (IBD) and colorectal cancer. However, its role in tumor immunity is unknown. Here, we report that decreased RIPK3 in colorectal cancer correlates with the accumulation of myeloid-derived suppressor cells (MDSC). Deficiency of RIPK3 boosted tumorigenesis via accumulation and immunosuppressive activity of MDSCs. Reduction of RIPK3 in MDSC and colorectal cancer cells elicited NFκB-transcribed COX-2, which catalyzed the synthesis of prostaglandin E2 (PGE2). PGE2 exacerbated the immunosuppressive activity of MDSCs and accelerated tumor growth. Moreover, PGE2 suppressed RIPK3 expression while enhancing expression of NFκB and COX-2 in MDSCs and colorectal cancer cells. Inhibition of COX-2 or PGE2 receptors reversed the immunosuppressive activity of MDSCs and dampened tumorigenesis. Patient databases also delineated the correlation of RIPK3 and COX-2 expression with colorectal cancer survival. Our findings demonstrate a novel signaling circuit by which RIPK3 and PGE2 regulate tumor immunity, providing potential ideas for immunotherapy against colorectal cancer.Significance: A novel signaling circuit involving RIPK3 and PGE2 enhances accumulation and immunosuppressive activity of MDSCs, implicating its potential as a therapeutic target in anticancer immunotherapy.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5586/F1.large.jpg Cancer Res; 78(19); 5586-99. ©2018 AACR.

Similar articles

See all similar articles

Cited by 10 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback