Related Experiment Video

Updated: Feb 8, 2026

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

Regulation of PD-L1: Emerging Routes for Targeting Tumor Immune Evasion

Yiting Wang¹, Huanbin Wang¹, Han Yao¹

¹MOH Key Laboratory of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Frontiers in Pharmacology

|June 19, 2018

Abstract:

Immune checkpoint blockade therapies (ICBTs) targeting programmed cell death 1 (PD-1) and its ligand programmed death ligand-1 (PD-L1/B7-H1/CD274) have exhibited momentous clinical benefits and durable responses in multiple tumor types. However, primary resistance is found in considerable number of cancer patients, and most responders eventually develop acquired resistance to ICBT. To tackle these challenges, it is essential to understand how PD-L1 is controlled by cancer cells to evade immune surveillance. Recent research has shed new light into the mechanisms of PD-L1 regulation at genetic, epigenetic, transcriptional, translational, and posttranslational levels. In this work, we systematically discuss the mechanisms that control the gene amplification, epigenetic alteration, transcription, subcellular transportation and posttranscriptional modification of PD-L1 in cancer cells. We further categorize posttranscriptional PD-L1 regulations by the molecular modification of PD-L1, including glycosylation, phosphorylation, ubiquitination, deubiquitination, and lysosomal degradation. These findings may provide new routes for targeting tumor immune escape and catalyze the development of small molecular inhibitors of PD-L1 in addition to existing antibody drugs.

Insights

Immune checkpoint blockade therapies (ICBTs) show promise, but resistance is common. Understanding programmed death ligand-1 (PD-L1) regulation in cancer is key to overcoming this resistance and improving treatments.

Area of Science:

Immunology
Oncology
Molecular Biology

Background:

Immune checkpoint blockade therapies (ICBTs) targeting programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) offer significant clinical benefits in cancer treatment.
However, primary and acquired resistance to ICBTs limits their effectiveness in a substantial number of patients.
Understanding the intricate mechanisms of PD-L1 regulation within cancer cells is crucial for overcoming immune evasion.

Purpose of the Study:

To systematically review and discuss the multifaceted mechanisms controlling PD-L1 expression in cancer cells.
To explore PD-L1 regulation across genetic, epigenetic, transcriptional, translational, and posttranslational levels.
To identify potential new therapeutic strategies targeting PD-L1 to enhance anti-tumor immunity.

Main Methods:

Comprehensive literature review of recent research on PD-L1 regulation.
Systematic discussion of mechanisms including gene amplification, epigenetic alterations, and transcriptional control.
Categorization of posttranscriptional modifications such as glycosylation, phosphorylation, ubiquitination, and degradation.

Main Results:

PD-L1 regulation is complex, occurring at multiple levels including genetic, epigenetic, transcriptional, and posttranscriptional modifications.
Posttranscriptional regulation involves diverse molecular modifications like glycosylation, phosphorylation, ubiquitination, deubiquitination, and lysosomal degradation.
These regulatory pathways offer insights into how cancer cells evade immune surveillance via PD-L1.

Conclusions:

A thorough understanding of PD-L1 regulation mechanisms is essential for developing strategies to overcome ICBT resistance.
Targeting these regulatory pathways may lead to novel therapeutic approaches, including small molecule inhibitors of PD-L1.
This knowledge can potentially enhance the efficacy of existing ICBTs and improve patient outcomes in cancer therapy.

Read full analysis

Keywords:

PD-L1 gene expression immunotherapy post-translational modification small molecular inhibitors

More Related Videos

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression

Published on: January 19, 2019

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Published on: September 25, 2018

Related Concept Videos

Routes of Persuasion

Routes of Persuasion

Persuasion is the process of changing our attitude toward something based on some kind of communication. Much of the persuasion we experience comes from outside forces. How do people convince others to change their attitudes, beliefs, and behaviors? What communications do you receive that attempt to persuade you to change your attitudes, beliefs, and behaviors?

Emerging Adulthood

Emerging Adulthood

Jeffrey Arnett's concept of emerging adulthood offers a framework to understand the unique developmental stage between adolescence and full-fledged adulthood, generally from ages 18 to 25. This period is marked by extensive exploration and shifts in identity, relationships, and career choices, a process known in psychology as role experimentation. Emerging adulthood reflects the evolving cultural expectations surrounding adulthood and the dynamic process of personal transformation during...

PD Controller: Design

PD Controller: Design

In automotive engineering, car suspension systems often employ Proportional Derivative (PD) controllers to enhance performance. PD controllers are utilized to adjust the damping force in response to road conditions. A controller, acting as an amplifier with a constant gain, demonstrates proportional control, with output directly mirroring input.
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...

What is the Immune System?

What is the Immune System?

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

Humoral Immune Responses

Humoral Immune Responses

Articles linked to this work by shared authors, journal, and citation graph.

Digital Healthy Aging in China: Current Landscape and the Way Forward.

Health care science·2026

Deprotonation and Alkylation of Weakly Acidic C(sp3)─H Bonds Through In Situ Generation of a Strong Hydride Base From 1,1,3,3-Tetramethyldisiloxane and Potassium tert-Butoxide.

Angewandte Chemie (International ed. in English)·2026

LC-MS/MS-based clinical value exploration of the methionine cycle in luminal breast cancer.

Oncology letters·2026

Efficacy and safety of the single-dose pegylated G-CSF vs. daily G-CSF for peripheral blood stem cells mobilization in donors: a multicenter, randomized controlled trial.

Frontiers in immunology·2026

Photocatalytic Remote Radical-Polar Crossover Reaction: Access of Organofluorine Compounds via 1,2-Carbonyl Migration.

Organic letters·2026

Hollow cubic-phase modulated radial coherent beam propagation in atmospheric turbulence: emission efficiency and echo enhancement with Cassegrain systems.

Optics express·2026

See all related articles