A distinct innate lymphoid cell population regulates tumor-associated T cells.
A distinct innate lymphoid cell population regulates tumor-associated T cells.
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DOI：
10.1038/nm.4278
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发表时间：
2017-03
期刊：
影响因子：
82.9
通讯作者：
Ohashi PS
中科院分区：
文献类型：
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作者：
Crome SQ;Nguyen LT;Lopez-Verges S;Yang SY;Martin B;Yam JY;Johnson DJ;Nie J;Pniak M;Yen PH;Milea A;Sowamber R;Katz SR;Bernardini MQ;Clarke BA;Shaw PA;Lang PA;Berman HK;Pugh TJ;Lanier LL;Ohashi PS
抗肿瘤T细胞受多种负调控机制的影响。最近发现先天淋巴样细胞（ILCs）调节适应性T细胞反应，这使我们研究了ILCs在癌症背景下的调节潜力。我们发现了一种独特的ILC群体，可以抑制来自高级别浆液性肿瘤的肿瘤浸润淋巴细胞（til），确定了它们在体外的抑制能力，并对它们的表型进行了全面分析。值得注意的是，TIL培养中CD56+CD3−群体的存在与T细胞数量减少有关，进一步的功能研究表明，该群体抑制TIL扩增并改变TIL细胞因子的产生。转录组分析和表型表征表明，调节性CD56+CD3−细胞表现出低细胞毒活性，产生IL-22，并且具有与自然杀伤（NK）细胞和其他ilc重叠的表达谱。NKp46在这些细胞中高度表达，将抗NKp46抗体添加到TIL培养物中可以消除这些调节性ilc抑制T细胞扩增的能力。值得注意的是，TIL培养物中这些调节性ilc的存在与疾病复发时间的显著减少相对应。这些研究表明，以前未表征的ILC群体调节肿瘤相关T细胞的活性和扩张。
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.