Details

Autor(en) / Beteiligte

• Hatzioannou, Aikaterini
• Nayar, Saba
• Gaitanis, Anastasios
• Barone, Francesca
• Anagnostopoulos, Constantinos
• Verginis, Panayotis

Titel

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

Ist Teil von

• Oncoimmunology, 2016-09, Vol.5 (9), p.e1216289-e1216289

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2016

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. Mechanistically, we demonstrate that PDPN + LNSCs mediate T cell growth arrest and induction of apoptosis to activated CD69 + CD4 + T cells. Importantly, LTbR-Ig-mediated blockade of PDPN + LNSCs expansion and function significantly attenuates melanoma tumor growth and enhances the infiltration and proliferation of CD4 + TILs. Overall, our findings decipher a novel role of PDPN-expressing LNSCs in the elimination of CD4 + TILs and propose a new target for tumor immunotherapy.