한빛사논문
- 조회568
Se-Hoon Lee 1,2, Yeongmin Kim 3, Bu-Nam Jeon 4, Gihyeon Kim 3,4, Jinyoung Sohn 4, Youngmin Yoon 3,5, Sujeong Kim 3, Yunjae Kim 3, Hyemin Kim 1,6, Hongui Cha 1,6, Na-Eun Lee 1,2, Hyunsuk Yang 4, Joo-Yeon Chung 4, A-Reum Jeong 4, Yun Yeon Kim 4, Sang Gyun Kim 4, Yeonhee Seo 7, Sehhoon Park 1, Hyun Ae Jung 1, Jong-Mu Sun 1, Jin Seok Ahn 1, Myung-Ju Ahn 1, Hansoo Park 3,4, Kyoung Wan Yoon 4
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea.
2Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, South Korea.
3Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, South Korea.
4Genome and Company, Pangyo-ro 253, Bundang-gu., Seoungnam-si, Gyeonggi-do, 13486, South Korea.
5Division of Nephrology, Department of Medicine, Chosun University Hospital, Chosun University School of Medicine, Gwangju, 61452, South Korea.
6Medical Research Institute, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea.
7NEX-I Inc., Seoul, 05854, South Korea.
S.-H.L., Ye.K., B.-N.J., and G.K. contributed equally to this work.
CORRESPONDING AUTHORS: Hansoo Park, Kyoung Wan Yoon
Abstract
Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non-small cell lung cancer treated with anti-programmed cell death protein-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule-1 (ICAM-1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM-1 (sICAM-1) is a key molecule that increases the efficacy of anti-PD-1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM-1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM-1-mediated anti-tumor pathway. Using sICAM-1 alone and in combination with anti-PD-1 enhances anti-tumor efficacy in anti-PD-1-responsive tumors in murine models. Notably, combinatorial therapy with sICAM-1 and anti-PD-1 converts anti-PD-1-resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM-1.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-27)
- 국내 연구진
- 생명과학 > 노화/암생물학
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