CD69+ Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma

被引:4
作者
You, Hongqin [1 ,2 ]
Wang, Yixin [1 ,2 ]
Wang, Xiaokun [2 ,3 ]
Zhu, Huifang [1 ,2 ]
Zhao, Yajie [2 ,4 ]
Qin, Peng [1 ,2 ]
Liu, Xue [1 ,2 ]
Zhang, Mengyu [1 ,2 ]
Fu, Xiaomin [1 ,2 ]
Xu, Benling [1 ,2 ]
Zhang, Yong [1 ,2 ]
Wang, Zibing [1 ,2 ]
Gao, Quanli [1 ,2 ]
机构
[1] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Dept Immunotherapy, Zhengzhou 450008, Peoples R China
[2] Henan Canc Hosp, Zhengzhou 450008, Peoples R China
[3] Zhengzhou Univ, Affiliated Canc Hosp, Dept Clin Lab, Zhengzhou 450008, Peoples R China
[4] Zhengzhou Univ, Affiliated Canc Hosp, Dept Breast, Zhengzhou 450008, Peoples R China
基金
中国国家自然科学基金;
关键词
V delta 1 gamma delta T cells; CD69; Hepatocellular carcinoma; Antitumor activity; MANAGEMENT; PATTERNS;
D O I
10.1016/j.molimm.2024.06.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background & aims: Hepatocellular carcinoma (HCC), one of the malignancies with a wide expression of stress ligands recognized by V delta 1 gamma delta T cells, has received much attention in adoptive immunotherapy of gamma delta T cells. In this study, we aimed to identify the potential anti-tumor V delta 1 gamma delta T subpopulations in HCC. Methods: Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University. Blood and tumor tissue samples were obtained respectively. Bioinformatics methods were used to analyze total gamma delta T cells and subsets infiltration, overall survival of HCC patients with high and low infiltration level of V delta 1 gamma delta T cells, and IFNG, granzyme A, granzyme B and perforin expression in TRDV1high/lowCD69high/low groups. CD69 expression and V delta 1 gamma delta T cells infiltration in HCC were detected by immunofluorescence. Phenotypic analysis of V delta 1 gamma delta T cells in blood and tumor tissue samples were performed by flow cytometry. Results: V delta 1 gamma delta T cells infiltrating in HCC were associated with better clinical outcome. Study in tumor microenvironment (TME) of HCC demonstrated that not total V delta 1 gamma delta T but CD69+ V delta 1 gamma delta subset infiltration was associated with smaller tumor volume. Moreover, HCC patients simultaneously with high TRDV1 and CD69 expression produced more effector molecules and had longer survival time. Since V delta 1 gamma delta T cells in the tumor microenvironment were often difficult to access, we demonstrated that CD69+ V delta 1 gamma delta T cells also existed in peripheral blood mononuclear cells (PBMC) of HCC and displayed enhanced cytotoxic potentials than HDs. Finally, we investigated the functions and found that CD69+ V delta 1 gamma delta T cells exhibited stronger tumor reactivities when challenged by tumor cells. Conclusions: CD69+ V delta 1 gamma delta T cells are functional V delta 1 gamma delta T cell subsets in patients with HCC. Circulating CD69+ V delta 1 gamma delta T cell is a promising candidate in immunotherapy of HCC.
引用
收藏
页码:76 / 84
页数:9
相关论文
共 50 条
[41]   Anti-tumor activity of KNTC2 siRNA in orthotopic tumor model mice of hepatocellular carcinoma [J].
Makita, Yukimasa ;
Murata, Shumpei ;
Katou, Yoshiki ;
Kikuchi, Kuniko ;
Uejima, Hiroshi ;
Teratani, Mika ;
Hoashi, Yasutaka ;
Kenjo, Eriya ;
Matsumoto, Satoru ;
Nogami, Masahiro ;
Otake, Kentaro ;
Kawamata, Yuji .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 493 (01) :800-806
[42]   Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma [J].
Lao, Yuanxiang ;
Cui, Xiaohan ;
Xu, Zhu ;
Yan, Hongyao ;
Zhang, Zechuan ;
Zhang, Zhenwei ;
Geng, Longpo ;
Li, Binghua ;
Lu, Yijun ;
Guan, Qifei ;
Pu, Xiaohong ;
Zhao, Suwen ;
Zhu, Jiapeng ;
Qin, Xihu ;
Sun, Beicheng .
JOURNAL OF HEPATOLOGY, 2024, 81 (05) :847-861
[43]   Anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice [J].
韩克起 ;
顾伟 ;
苏永华 ;
张亚妮 ;
黄雪强 ;
刘岭 ;
王喜 ;
凌昌全 .
Journal of Medical Colleges of PLA, 2004, (06) :338-341+345
[44]   Anti-Tumor Effects of Carrimycin and Monomeric Isovalerylspiramycin I on Hepatocellular Carcinoma in Vitro and in Vivo [J].
Jin, Yong ;
Zuo, Hong Xiang ;
Li, Ming Yue ;
Zhang, Zhi Hong ;
Xing, Yue ;
Wang, Jing Ying ;
Ma, Juan ;
Li, Gao ;
Piao, Hongxin ;
Gu, Puqing ;
Jin, Xuejun .
FRONTIERS IN PHARMACOLOGY, 2021, 12
[45]   Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma [J].
Zhou, Meiling ;
Yi, Youping ;
Liu, Li ;
Lin, Yan ;
Li, Jian ;
Ruan, Jinghua ;
Zhong, Zhirong .
JOURNAL OF CANCER, 2019, 10 (23) :5820-5831
[46]   Synergistic Anti-Tumor Effects of Zoledronic Acid and Radiotherapy against Metastatic Hepatocellular Carcinoma [J].
Morii, Kazuhiko ;
Aoyama, Yuhki ;
Nakamura, Shinichiro ;
Okushin, Hiroaki .
INTERNAL MEDICINE, 2015, 54 (20) :2609-2613
[47]   Combined anti-tumor effects of IFN-α and sorafenib on hepatocellular carcinoma in vitro and in vivo [J].
Wang, Lijing ;
Jia, Dongwei ;
Duan, Fangfang ;
Sun, Zhichao ;
Liu, Xiaojuan ;
Zhou, Lei ;
Sun, Linlin ;
Ren, Shifang ;
Ruan, Yuanyuan ;
Gu, Jianxin .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 422 (04) :687-692
[48]   Anti-malarial atovaquone exhibits anti-tumor effects by inducing DNA damage in hepatocellular carcinoma [J].
Gao, Xiaoge ;
Liu, Xiangye ;
Shan, Wenhua ;
Liu, Qian ;
Wang, Chao ;
Zheng, Jiwei ;
Yao, Hong ;
Tang, Renxian ;
Zheng, Junnian .
AMERICAN JOURNAL OF CANCER RESEARCH, 2018, 8 (09) :1697-1711
[49]   Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway [J].
Wang, Haina ;
Wang, Rui ;
Huang, Dan ;
Li, Sihan ;
Gao, Beibei ;
Kang, Zhijie ;
Tang, Bo ;
Xie, Jiajun ;
Yan, Fanzhi ;
Liang, Rui ;
Li, Hua ;
Yan, Jinsong .
FRONTIERS IN PHARMACOLOGY, 2021, 12
[50]   Pharmacological inhibition of Frizzled-7 displays anti-tumor properties in hepatocellular carcinoma [J].
Nambotin, Sarah Beseme ;
Lefrancois, Lydie ;
Sainsily, Xavier ;
Berthillon, Pascale ;
Kim, Miran ;
Wands, Jack R. ;
Chevallier, Michele ;
Jalinot, Pierre ;
Scoazec, Jean-Yves ;
Trepo, Christian ;
Zoulim, Fabien ;
Merle, Philippe .
JOURNAL OF HEPATOLOGY, 2011, 54 (02) :288-299