A subset of Th1 cells expressing Foxp3, named Th1-Tregs, have been identified in tumors, but the mechanisms underlying their accumulation in tumors are unclear. Using single-cell and bulk RNA sequencing, Kuratani and colleagues identify the chemokine platelet factor 4 (PF4) as a polarizing factor for Th1-Tregs. PF4 is shown to be made by Arg1+ tumor-associated macrophages, and these cells contribute to lowered antitumoral activity. Genetic deletion or antibody neutralization of PF4 in tumor-bearing mice reduces Th1-Treg frequencies and tumor growth. Targeting of this subset of Tregs, instead of all Tregs, may lead to tumor clearance with limited risk of inducing autoimmunity.
Kuratani A, …, Yamamoto M. Science 2024 Nov 22;386,eadn8608.
How secreted factors...