한빛사 논문
Jaemoon Koh1, 2, Hye Young Kim3, Youngha Lee4, In Kyu Park5, Chang Hyun Kang5, Young Tae Kim5, Ji Eun Kim6 , Murim Choi4, Won-Woo Lee4,7, Yoon Kyung Jeon1, and Doo Hyun Chung1,2,*
1 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
2 Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
3 Laboratory of Mucosal Immunity in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
4 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
5 Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Korea
6 Department of Pathology, Seoul Metropolitan Government Boramae Hospital, Seoul, Korea
7 Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea
*Corresponding Author:Doo Hyun Chung
Department of Pathology, Seoul National University College of Medicine, Laboratory of Immune Regulation, Department of Biosciences, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Abstract
Purpose:The plasticity of ILC has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In the present study, we explored plasticity of ILCs in human lung cancer. Experimental Design: We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in co-culture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 lung cancer patients. Results: Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCCs) but not adenocarcinomas (ADCs). In non-small cell lung cancers, the percentage of ILC3 was associated with IL-23 expression in tumor cells but not immune cells. In co-cultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL-23, thus promoting IL-17-mediated tumor cell proliferation. Consistently, among IL-17+ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3-RORgt+ ILC3, IL-17 expression level, and IL-23- or IL-17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC. Conclusions: Conversion from ILC1 into ILC3 by IL-23-producing SqCCs promotes IL-17-mediated tumor progression, resulting in a poor prognosis.
Keywords: ILC, plasticity, tumor microenvironment, IL-17, IL-23, lung cancer, human
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