A distinct innate lymphoid cell population regulates tumor-associated T cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-02-06

AUTHORS

Sarah Q Crome, Linh T Nguyen, Sandra Lopez-Verges, S Y Cindy Yang, Bernard Martin, Jennifer Y Yam, Dylan J Johnson, Jessica Nie, Michael Pniak, Pei Hua Yen, Anca Milea, Ramlogan Sowamber, Sarah Rachel Katz, Marcus Q Bernardini, Blaise A Clarke, Patricia A Shaw, Philipp A Lang, Hal K Berman, Trevor J Pugh, Lewis L Lanier, Pamela S Ohashi

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. More... »

PAGES

368-375

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.4278

DOI

http://dx.doi.org/10.1038/nm.4278

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083686097

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28165478


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