Koh Jaemoon, Kim Hye Young, Lee Youngha, Park In Kyu, Kang Chang Hyun, Kim Young Tae, Kim Ji-Eun, Choi Murim, Lee Won-Woo, Jeon Yoon Kyung, Chung Doo Hyun
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Clin Cancer Res. 2019 Jul 1;25(13):4026-4037. doi: 10.1158/1078-0432.CCR-18-3458. Epub 2019 Apr 12.
The plasticity of innate lymphoid cells (ILCs) has been reported and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In this study, we explored plasticity of ILCs in human lung cancer.
We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in coculture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 patients with lung cancer.
Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCC) but not adenocarcinomas (ADC). In non-small-cell lung cancers, the percentage of ILC3 was associated with IL23 expression in tumor cells but not immune cells. In cocultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL23, thus promoting IL17-mediated tumor cell proliferation. Consistently, among IL17 immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3RORγt ILC3, IL17 expression level, and IL23- or IL17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC.
Conversion from ILC1 into ILC3 by IL23-producing SqCCs promotes IL17-mediated tumor progression, resulting in a poor prognosis.
已有报道称固有淋巴细胞（ILC）具有可塑性，且在肠道微环境中存在这种现象。然而，ILC的可塑性是否有助于调节肿瘤微环境仍不清楚。在本研究中，我们探索了人肺癌中ILC的可塑性。
我们分析了从80例患者新鲜获取的肺癌中的免疫亚群和细胞因子表达，并研究了在与肺癌细胞共培养时ILC1向ILC3的转化。由875例肺癌患者组成的回顾性队列评估了转化后的ILC3及其相关通路的预后影响。
在肺鳞状细胞癌（SqCC）中发现ILC1的百分比低，ILC3的百分比高，而在腺癌（ADC）中则不然。在非小细胞肺癌中，ILC3的百分比与肿瘤细胞而非免疫细胞中的IL23表达相关。在共培养中，SqCC的肿瘤细胞通过产生IL23将ILC1转化为ILC3，从而促进IL17介导的肿瘤细胞增殖。同样，在IL17免疫细胞中，SqCC中ILC的百分比高于ADC。此外，CD3RORγt ILC3的数量、IL17表达水平以及表达IL23或IL17RA的肿瘤细胞与SqCC患者而非ADC患者的生存期短相关。
产生IL23的SqCC将ILC1转化为ILC3可促进IL17介导的肿瘤进展，导致预后不良。
