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

作者：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^*

来源：Nature Medicine, 2017, 23(3): 368-375.

DOI：10.1038/nm.4278

Antitumor T cells are subject to multiple mechanisms of negative regulation(1-3). Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses(4-6) 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.

• 出版日期2017-3