Non-cytomembrane PD-L1: An atypical target for cancer

Honggang Ying; Xiaozhen Zhang; Yi Duan; Mengyi Lao; Jian Xu; Hanshen Yang; Tingbo Liang; Xueli Bai

doi:10.1016/j.phrs.2021.105741

Non-cytomembrane PD-L1: An atypical target for cancer

Pharmacol Res. 2021 Aug:170:105741. doi: 10.1016/j.phrs.2021.105741. Epub 2021 Jun 24.

Authors

Honggang Ying¹, Xiaozhen Zhang¹, Yi Duan¹, Mengyi Lao¹, Jian Xu¹, Hanshen Yang¹, Tingbo Liang², Xueli Bai³

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou 310003, Zhejiang, China.
² Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou 310003, Zhejiang, China. Electronic address: [email protected].
³ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, Hangzhou 310003, Zhejiang, China. Electronic address: [email protected].

PMID: 34174446
DOI: 10.1016/j.phrs.2021.105741

Abstract

Programmed death ligand 1 (PD-L1) has conventionally been considered as a type I transmembrane protein that can interact with its receptor, programmed cell death 1 (PD-1), thus inducing T cell deactivation and immune escape. However, targeting the PD-1/PD-L1 axis has achieved adequate clinical responses in very few specific malignancies. Recent studies have explored the extracellularly and subcellularly located PD-L1, namely, nuclear PD-L1 (nPD-L1), cytoplasmic PD-L1 (cPD-L1), soluble PD-L1 (sPD-L1), and extracellular vesicle PD-L1 (EV PD-L1), which might shed light on the resistance to anti-PD1/PDL1 therapy. In this review, we summarize the four atypical localizations of PD-L1 with a focus on their novel functions, such as gene transcription regulation, therapeutic efficacy prediction, and resistance to various cancer therapies. Additionally, we highlight that non-cytomembrane PD-L1s are of significant cancer diagnostic value and are promising therapeutic targets to treat cancer.

Keywords: Actinomycin D (PubChem CID: 457193); BMS-1001 (PubChem CID: 145925650); BMS-1166 (PubChem CID: 118434635); Cancer target; Cytoplasmic PD-L1; Daunorubicin (PubChem CID: 30323); Doxorubicin (PubChem CID: 31703); Epirubicin (PubChem CID: 41867); Extracellular vesicle PD-L1; H1A (PubChem CID: 101144265); Non-cytomembrane PD-L1; Nuclear PD-L1; Santacruzamate A (PubChem CID: 72946782); Soluble PD-L1.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
B7-H1 Antigen / antagonists & inhibitors*
B7-H1 Antigen / metabolism
Humans
Immune Checkpoint Inhibitors / adverse effects
Immune Checkpoint Inhibitors / therapeutic use*
Molecular Targeted Therapy
Neoplasms / drug therapy*
Neoplasms / immunology
Neoplasms / metabolism
Signal Transduction
Tumor Microenvironment

Substances

B7-H1 Antigen
CD274 protein, human
Immune Checkpoint Inhibitors