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

doi:10.1016/j.ebiom.2022.103987

Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy

EBioMedicine. 2022 May:79:103987. doi: 10.1016/j.ebiom.2022.103987. Epub 2022 Apr 16.

Authors

Honggang Ying¹, Jian Xu¹, Xiaozhen Zhang¹, Tingbo Liang², Xueli Bai³

Affiliations

¹ 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.
² 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. Electronic address: liangtingbo@zju.edu.cn.
³ 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. Electronic address: shirleybai@zju.edu.cn.

Abstract

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.

Keywords: Cancer immunotherapy; HHLA2; Immune checkpoint; KIR3DL3; TMIGD2.

Publication types

Review

MeSH terms

Endogenous Retroviruses* / genetics
Humans
Immune Checkpoint Proteins*
Immunoglobulins* / genetics
Immunotherapy
Neoplasms* / drug therapy
Neoplasms* / genetics
Terminal Repeat Sequences

Substances

HHLA2 protein, human
Immune Checkpoint Proteins
Immunoglobulins