Intratumoral accumulation of podoplanin-expressing lymph node stromal cells promote tumor growth through elimination of CD4⁺ tumor-infiltrating lymphocytes.

ABSTRACT: The beneficial effects of checkpoint blockade in tumor immunotherapy are limited to patients with increased tumor-infiltrating lymphocytes (TILs). Delineation of the regulatory networks that orchestrate the presence of TILs holds great promise for the design of effective immunotherapies. Podoplanin/gp38 (PDPN)-expressing lymph node stromal cells (LNSCs) are present in tumor stroma; however, their effect in the regulation of TILs remains elusive. Herein we demonstrate that intratumor injection of ex-vivo-isolated PDPN⁺ LNSCs into melanoma-bearing mice induces elimination of TILs and promotes tumor growth. In support, PDPN⁺ LNSCs exert their function through direct inhibition of CD4⁺ T cell proliferation in a cell-to-cell contact independent fashion. Mechanis

SUBMITTER: Hatzioannou A 

PROVIDER: S-EPMC5048774 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature