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Nat Med. 2017 Mar;23(3):368-375. doi: 10.1038/nm.4278. Epub 2017 Feb 6.

A distinct innate lymphoid cell population regulates tumor-associated T cells.

Author information

1
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
2
Department of Microbiology and Immunology and the Parker Institute for Cancer Immunotherapy, University of California San Francisco, San Francisco, California, USA.
3
Gorgas Memorial Institute of Health Studies, Panama City, Panama.
4
Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada.
5
Division of Gynecologic Oncology, University Health Network, Toronto, Ontario, Canada.
6
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
7
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Abstract

Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3- cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

PMID:
28165478
PMCID:
PMC5497996
DOI:
10.1038/nm.4278
[Indexed for MEDLINE]
Free PMC Article

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