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Cancer Discov. 2019 Jul 2. pii: CD-19-0161. doi: 10.1158/2159-8290.CD-19-0161. [Epub ahead of print]

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

Author information

1
S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine.
2
Department of Surgery and Cell Biology, New York University School of Medicine.
3
Cell, Developmental & Cancer Biology, Oregon Health & Science University.
4
Molecular and Medical Genetics, Oregon Health and Science University.
5
Computational Biology Program, Oregon Health & Science University.
6
Computational Biology Program, Oregon Health & Science University, Knight Cancer Institute.
7
Applied Bioinformatics Laboratories, New York University School of Medicine.
8
Moffit Cancer Center.
9
Department of Basic Science and Craniofacial Biology, New York University College of Dentistry.
10
Pathology, NYU Langone Health.
11
Perlmutter Cancer Center, New York University Langone Medical Center.
12
Department of Surgery and Cell Biology, New York University School of Medicine george.miller@nyumc.org.

Abstract

Unconventional T lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4-CD8-NK1.1- innate αβ T-cells (iαβTs) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ~10% of T-lymphocytes infiltrating PDA in mice and humans. Intra-tumoral iαβTs express a distinct TCR-repertoire and profoundly immunogenic phenotype compared to their peripheral counterparts and conventional lymphocytes. iαβTs comprised ~75% of the total intra-tumoral IL-17+ cells. Moreover, iαβT cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show iαβT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T cell expansion/activation and tumor protection. Collectively, iαβTs govern fundamental intra-tumoral crosstalk between innate and adaptive immune populations and are attractive therapeutic targets.

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