한빛사논문
- 조회438
Park, Jong Geun1; Roh, Pu Reun1; Kang, Min Woo1; Cho, Sung Woo1; Hwangbo, Suhyun2; Jung, Hae Deok3; Kim, Hyun Uk3,4; Kim, Ji Hoon1,5; Yoo, Jae-Sung1,6; Han, Ji Won1,6; Jang, Jeong Won1,6; Choi, Jong Young1,6; Yoon, Seung Kew1,6; You, Young Kyoung7; Choi, Ho Joong7; Ryu, Jae Yong4,8; Sung, Pil Soo1,6
1The Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea
2Department of Genomic Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
3Department of Chemical and Biomolecular Engineering (BK21 four), Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
4Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon 34141, Republic of Korea; Systems Biology and Medicine Laboratory
5Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 11765, Republic of Korea
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
7Department of Surgery, The Catholic University of Korea, Seoul, Republic of Korea
8Department of Biotechnology, Duksung Women’s University, 33 Samyang-ro 144-gil, Dobong-gu, Seoul 01369, Korea
Correspondence Pil Soo Sung, Ho Joong Choi, Jae Yong Ryu
Abstract
Background and aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment (TME). Immunoglobulin A (IgA) contributes to inflammation and dismantling anti-tumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in the TME of hepatocellular carcinoma (HCC).
Approach and results: CAF dynamics in HCC TME were analyzed via single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of advanced HCC patients treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels (p<0.05). Single-cell analysis showed that sub-cluster proportions in the CAF-fibroblast activation protein-α (FAP) matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of FAP in the CD68+ cells from patients with high serum IgA levels (p<0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 (PD-L1) expression levels than those in mock-treated CAFs (p<0.05). Co-culture with CAFs attenuated cytotoxic function of activated CD8+ T cells. Interestingly, activated CD8+ T cells co-cultured with IgA-treated CAFs exhibited increased programmed death-1 (PD-1) expression levels than those co-cultured with mock-treated CAFs (p<0.05).
Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T cell function. Our study highlighted their potential roles in tumor progression and immune suppression.
논문정보
- Research article
- 2024년 02월 (BRIC 등록일 2024-03-12)
- 국내 연구진
- 의약학 > 면역의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
