Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity.

ABSTRACT: Metastatic dissemination remains a significant barrier to successful therapy for melanoma. Wnt5A is a potent driver of invasion in melanoma and is believed to be secreted from the tumor microenvironment (TME). Our data suggest that myeloid-derived suppressor cells (MDSC) in the TME are a major source of Wnt5A and are reliant upon Wnt5A for multiple actions. Knockdown of Wnt5A specifically in the myeloid cells demonstrated a clear decrease in Wnt5A expression within the TME in vivo as well as a decrease in intratumoral MDSC and regulatory T cell (Treg). Wnt5A knockdown also decreased the immunosuppressive nature of MDSC and decreased expression of TGFβ1 and arginase 1. In the presence of Wnt5A-depleted MDSC, tumor-infiltrating lymphocytes expressed decreased PD-1 and LAG3, suggesting

SUBMITTER: Douglass SM 

PROVIDER: S-EPMC8330365 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature