John Gordon: Researchers identified a substantial presence of peripherally induced Treg cells in TME
John Gordon, Co-Founder, Director and VP of Scientific Affairs at Celentyx, shared a post on LinkedIn about a paper by Sang-Nee Tan et al. published in the Journal of Experimental Medicine:
“Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39”
Authors: Sang-Nee Tan, Jing Hao, Jing Ge, Ling Ni, Chen Dong et al.
“Breaking Study at the Rockefeller University Press JExpMed reveals how Tregs develop in the TME to suppress anti-Tumour Immunity via CD39.
‘Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39’.
Regulatory T (Treg) cells are known to impede antitumor immunity, yet the regulatory mechanisms and functional roles of these cells remain poorly understood.
In this study, through the characterization of multiple cancer models, researchers identified a substantial presence of peripherally induced Treg cells in the tumor microenvironment (TME). Depletion of these cells triggered antitumor responses and provided potent therapeutic effects by increasing functional CD8+ T cells.
Fate-mapping and transfer experiments revealed that IFN-γ–expressing T helper (Th) 1 cells differentiated into Treg cells in response to TGF-β signalling in tumors. Pseudotime trajectory analysis further revealed the terminal differentiation of Th1-like Treg cells from Th1 cells in the TME.
Tumor-resident Treg cells highly expressed T-bet, which was essential for their functions in the TME. Additionally, CD39 was highly expressed by T-bet+ Treg cells in both mouse and human tumors, and was necessary for Treg cell-mediated suppression of CD8+ T cell responses.
This study elucidated the developmental pathway of intratumoral Treg cells and highlighted novel strategies for targeting them in cancer patients.
Figure – A perspective on targeting CD39 in combination with other cancer therapies – Taken from ‘Targeting CD39 in cancer’ – Achim Moesta, Xian-Yang Li and Mark Smyth.”
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