Recent Findings in the Regulation of Programmed Death Ligand 1 Expression.

Xiangfeng Shen,Lihong Zhang,Yulin Li,Jicheng Li,Yishu Wang,Zhi-Xiang Xu

doi:10.3389/fimmu.2019.01337

Abstract

With the recent approvals for the application of monoclonal antibodies that target the well-characterized immune checkpoints, immune therapy shows great potential against both solid and hematologic tumors. The use of these therapeutic monoclonal antibodies elicits inspiring clinical results with durable objective responses and improvements in overall survival. Agents targeting programmed cell death protein 1 (PD-1; also known as PDCD1) and its ligand (PD-L1) achieve a great success in immune checkpoints therapy. However, the majority of patients fail to respond to PD-1/PD-L1 axis inhibitors. Expression of PD-L1 on the membrane of tumor and immune cells has been shown to be associated with enhanced objective response rates to PD-1/PD-L1 inhibition. Thus, an improved understanding of how PD-L1 expression is regulated will enable us to better define its role as a predictive marker. In this review, we summarize recent findings in the regulation of PD-L1 expression.

Highlights

With rapid development of immunotherapy for cancer treatment in decades, immune checkpoint therapy that mediates tumor cell death through the reactivated immune system has become the most attractive strategy for cancer therapy due to their impressive therapeutic efficacy
We summarize recent findings in the regulation of PD-L1 expression
Despite considerable improvement of cancer therapy, which has been achieved through PD-1/PD-L1 blockade, the knowledge regarding the biology of these regulators in cancer immune surveillance is still relatively limited

Summary

Introduction

With rapid development of immunotherapy for cancer treatment in decades, immune checkpoint therapy that mediates tumor cell death through the reactivated immune system has become the most attractive strategy for cancer therapy due to their impressive therapeutic efficacy. −, negative; +, positive; NC, not change; IR, irradiation; UVR, ultraviolet radiation; CRC, colorectal cancer; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinomas; NSCLC, non-small cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; HPKs, human primary keratinocytes; HPMs, human primary melanocytes; AML, acute myeloid leukemia; SCLC, small cell lung cancer; NHL, non-Hodgkin’s lymphoma; CSCs, cancer stem-like cells; sPD-L1, soluable programmed death ligand-1; IFN-γ, interferon-γ; EGFR, epidermal growth factor receptor; JAK2, Janus kinase 2; AXL, tyrosine-protein kinase receptor UFO;IL-6, interleukin-6; STAT3, signal transducer and activator of transcription 3; ATM, ataxia telangiectasia mutated; ATR, ataxia telangiectasia and Rad3-related protein; IRF-1, interferon-responsive factor 1; NRF2, nuclear factor E2-related transcription factor 2;MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; EMT, epithelial-mesenchymal transition; FASN, fatty acid synthase; TGFβ1, transforming growth factor β1; Akt, protein kinase B; NF-κB, nuclear factor kappa B; PI3K, phosphatidylinositol 3 kinase; DNMT1, DNA methyltransferase 1; KIT, receptor tyrosine kinase; GM-CSF, granulocyte macrophage colony-stimulating factor; CKS1B, CDC28 protein kinase regulatory subunit 1B.

Results

Conclusion