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

  • Author(s): Crome, Sarah Q;
  • Nguyen, Linh T;
  • Lopez-Verges, Sandra;
  • Yang, SY 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
  • et al.

Published Web Location

https://doi.org/10.1038/nm.4278
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.

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