Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy
Honggang Ying,
Jian Xu,
Xiaozhen Zhang,
Tingbo Liang,
Xueli Bai
Affiliations
Honggang Ying
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, , 79 Qingchun Road, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Innovation Centre for the Study of Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Clinical Research Centre for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Cancer Centre, Zhejiang University, Hangzhou, Zhejiang 310058, China
Jian Xu
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, , 79 Qingchun Road, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Innovation Centre for the Study of Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Clinical Research Centre for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Cancer Centre, Zhejiang University, Hangzhou, Zhejiang 310058, China
Xiaozhen Zhang
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, , 79 Qingchun Road, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Innovation Centre for the Study of Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Clinical Research Centre for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Cancer Centre, Zhejiang University, Hangzhou, Zhejiang 310058, China
Tingbo Liang
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, , 79 Qingchun Road, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Innovation Centre for the Study of Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Clinical Research Centre for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Cancer Centre, Zhejiang University, Hangzhou, Zhejiang 310058, China; Corresponding authors at: Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Xueli Bai
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, , 79 Qingchun Road, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Innovation Centre for the Study of Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Clinical Research Centre for the Study of Hepatobiliary & Pancreatic Diseases, Hangzhou, Zhejiang 310003, China; Cancer Centre, Zhejiang University, Hangzhou, Zhejiang 310058, China; Corresponding authors at: Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Summary: Human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2) is a newly emerging immune checkpoint that belongs to B7 family. HHLA2 has a co-stimulatory receptor transmembrane and immunoglobulin domain containing 2 (TMIGD2) and a newly discovered co-inhibitory receptor killer cell Ig-like receptor, three Ig domains, and long cytoplasmic tail (KIR3DL3), which endows it with both immunostimulant and immunosuppression functions in cancer development. In this review, we summarize the HHLA2 expression profile in human cancers, its association with cancer prognosis and clinical features, and its dual roles in regulating cancer immune response through up-to-date literatures. Furthermore, we highlight that precision cancer immunotherapy through manipulating HHLA2-KIR3DL3/TMIGD2 interaction is a promising antitumour strategy.
