Innate αß T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming.
Cancer Discov
; 9(9): 1288-1305, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31266770
ABSTRACT
Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαß+CD4-CD8-NK1.1- innate αß T cells (iαßT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαßTs represent â¼10% of T lymphocytes infiltrating PDA in mice and humans. Intratumoral iαßTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαßTs comprised â¼75% of the total intratumoral IL17+ cells. Moreover, iαßT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαßT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T-cell expansion/activation and tumor protection. Collectively, iαßTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets. SIGNIFICANCE:
We found that iαßTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαßTs induce a CCR5-dependent immunogenic tumor-associated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy.See related commentary by Banerjee et al., p. 1164.This article is highlighted in the In This Issue feature, p. 1143.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Linfócitos T
/
Receptores de Antígenos de Linfócitos T alfa-beta
/
Carcinoma Ductal Pancreático
/
Macrófagos
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Discov
Ano de publicação:
2019
Tipo de documento:
Article