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

Crome, Sarah Q; Nguyen, Linh T; Lopez-Verges, Sandra; Yang, S Y Cindy; Martin, Bernard; Yam, Jennifer Y; Johnson, Dylan J; Nie, Jessica; Pniak, Michael; Yen, Pei Hua; Milea, Anca; Sowamber, Ramlogan; Katz, Sarah Rachel; Bernardini, Marcus Q; Clarke, Blaise A; Shaw, Patricia A; Lang, Philipp A; Berman, Hal K; Pugh, Trevor J; Lanier, Lewis L; Ohashi, Pamela S.
Nat Med; 23(3): 368-375, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28165478
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.
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