Innate αβ T cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming

摘要: Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role TCRαβ+CD4-CD8-NK1.1- innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% lymphocytes infiltrating PDA mice and humans. Intratumoral express a distinct T-cell receptor repertoire profoundly immunogenic phenotype compared with their peripheral counterparts conventional lymphocytes. comprised ∼75% total intratumoral IL17+ cells. Moreover, iαβT-cell adoptive transfer is protective both murine models human organotypic systems. show iαβT induce CCR5-dependent macrophage reprogramming, thereby enabling marked CD4+ CD8+ expansion/activation protection. Collectively, govern fundamental cross-talk between adaptive immune attractive therapeutic targets. SIGNIFICANCE: activated subset slow growth disease. tumor-associated program, activation expansion, should be considered novel targets for immunotherapy.See related commentary by Banerjee et al., p. 1164.This article highlighted In This Issue feature, 1143.