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Updated: Jan 30, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Programmed cell death-1/programmed cell death ligand-1 checkpoint inhibitors: differences in mechanism of action
Ni Zhang1, Jingyao Tu2, Xue Wang1
1Department of Thoracic Surgery, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, Hubei, China.
Abstract:
Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors are widely used in many types of solid tumors, and are often considered to be in the same immunotherapy subclass. This review explores whether specific agents in these two categories exhibit differences in their mechanism of action, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety. Due to the complicated functional pathways in the immune checkpoint system, the epitopes, interfaces and signal pathways between PD-1: PD-L1/PD-L2, PD-L1/CD28/CTLA-4: B7-1 axes often overlap and affect each other. Therefore, the mechanisms of action of PD-1 and PD-L1 inhibitors reflect the corresponding cross connectivity and their unique characteristics. Only head-to-head comparative studies can provide definitive information regarding clinical efficacy and safety differences between specific PD-1/PD-L1 inhibitors.
Insights
This review examines differences between Programmed Cell Death-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) inhibitors in cancer immunotherapy. It highlights the need for head-to-head studies to clarify their distinct clinical efficacy and safety profiles.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors are a key class of cancer immunotherapies used across various solid tumors.
- These agents are often grouped into a single subclass, yet their distinct mechanisms and clinical outcomes warrant closer examination.
Purpose of the Study:
- To investigate potential differences in the mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety between PD-1 and PD-L1 inhibitors.
- To explore the complex interplay within the immune checkpoint system, including PD-1:PD-L1/PD-L2 and PD-L1/CD28/CTLA-4:B7-1 axes, and their influence on inhibitor characteristics.
Main Methods:
- This review synthesizes existing literature and comparative data on PD-1 and PD-L1 inhibitors.
- It analyzes the functional pathways and cross-connectivity within the immune checkpoint system.
Main Results:
- The mechanisms of action for PD-1 and PD-L1 inhibitors are influenced by overlapping and interconnected pathways within the immune checkpoint system.
- Specific agents within these categories may possess unique characteristics affecting their performance.
Conclusions:
- Direct head-to-head comparative studies are essential to definitively establish clinical efficacy and safety differences between individual PD-1 and PD-L1 inhibitors.
- Understanding these distinctions is crucial for optimizing cancer immunotherapy strategies.
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