Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.
Front Immunol. 2021 Jun 14;12:680055. doi: 10.3389/fimmu.2021.680055. eCollection 2021.
There is increasing evidence that group 2 innate lymphoid cells (ILC2s) play an essential role in allergy and parasitic infection. However, the role of ILC2s in human lung cancer remains unclear.
ILC2s from peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HDs) and non-small cell lung cancer (NSCLC) patients, and NSCLC tumor tissues were analyzed multicolor flow cytometry. ILC2s or CD14 cells were sorted by fluorescence-activated cell sorting. qPCR and flow cytometry were performed to assess the gene and protein expression of the indicated molecules. M1-like and M2-like macrophages were induced from CD14 monocytes .
ILC2s were significantly more enriched in PBMCs and tumor tissues from NSCLC patients than in HDs. After screening for the main immune checkpoint molecules, we found that PD-1 was upregulated in ILC2s in NSCLC patients. Functionally, PD-1 ILC2s from tumor tissues expressed higher levels of IL-4 and IL-13 regarding both mRNA and protein levels than PD-1 ILC2s. Furthermore, PD-1 ILC2s robustly boosted M2-like macrophage polarization , by secreting IL-4 and IL-13, while neutralization of IL-4 and IL-13 by antibodies abrogated M2-like macrophage polarization.
ILC2s are enriched in NSCLC patients and upregulate PD-1 expression. Upregulation of PD-1 facilitates the immunosuppressive function of ILC2s. PD-1 ILC2s enhance M2-like macrophage polarization by secreting IL-4 and IL-13. PD-1 acts as a positive regulator of the immunosuppressive function of ILC2s in human NSCLC.
越来越多的证据表明，2 型固有淋巴细胞（ILC2）在过敏和寄生虫感染中发挥着重要作用。然而，ILC2 在人类肺癌中的作用尚不清楚。
通过多色流式细胞术分析来自健康供体（HD）和非小细胞肺癌（NSCLC）患者的外周血单核细胞（PBMC）和 NSCLC 肿瘤组织中的 ILC2。通过荧光激活细胞分选对 ILC2 或 CD14 细胞进行分选。qPCR 和流式细胞术用于评估指示分子的基因和蛋白表达。从 CD14 单核细胞诱导 M1 样和 M2 样巨噬细胞。
与 HD 相比，NSCLC 患者的 PBMC 和肿瘤组织中 ILC2 明显更为丰富。在筛选主要免疫检查点分子后，我们发现 NSCLC 患者的 ILC2 中 PD-1 上调。功能上，与 PD-1 ILC2 相比，来自肿瘤组织的 PD-1 ILC2 在 mRNA 和蛋白水平上均表达更高水平的 IL-4 和 IL-13。此外，PD-1 ILC2 通过分泌 IL-4 和 IL-13 强烈促进 M2 样巨噬细胞极化，而通过抗体中和 IL-4 和 IL-13 则阻断了 M2 样巨噬细胞极化。
ILC2 在 NSCLC 患者中富集，并上调 PD-1 表达。PD-1 的上调促进了 ILC2 的免疫抑制功能。PD-1 通过分泌 IL-4 和 IL-13 增强 M2 样巨噬细胞极化。PD-1 作为人类 NSCLC 中 ILC2 免疫抑制功能的正调节剂。
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