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A snapshot of the PD-1/PD-L1 pathway
Chinmoy Ghosh1, Gary Luong1, Yue Sun1
1Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract:
Cancer cells can evade the attack from host immune systems via hijacking the regulatory circuits mediated by immune checkpoints. Therefore, reactivating the antitumor immunity by blockade of immune checkpoints is considered as a promising strategy to treat cancer. Programmed death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) are critical immune checkpoint proteins that responsible for negative regulation of the stability and the integrity of T-cell immune function. Anti-PD-1/PD-L1 drugs have been developed for immune checkpoint blockade and can induce clinical responses across different types of cancers, which provides a new hope to cure cancer. However, the patients' response rates to current anti-PD-1 or anti-PD-L1 therapies are still low and many initial responders finally develop resistance to these therapies. In this review, we provides a snapshot of the PD-1/PD-L1 molecular structure, mechanisms controlling their expression, signaling modulated by PD-1/PD-L1, current anti-PD-1/PD-L1 therapies, and the future perspectives to overcome the resistance.
Insights
Immune checkpoints like programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) help cancer evade immunity. Blocking these checkpoints offers cancer treatment hope, but resistance remains a challenge.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cancer cells evade immune detection by exploiting immune checkpoints.
- Immune checkpoints, such as programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), suppress anti-tumor immune responses.
- Blockade of these immune checkpoints is a promising cancer treatment strategy.
Purpose of the Study:
- To review the molecular structure and expression mechanisms of PD-1/PD-L1.
- To summarize the signaling pathways modulated by PD-1/PD-L1.
- To discuss current anti-PD-1/PD-L1 therapies and strategies to overcome resistance.
Main Methods:
- Literature review of PD-1/PD-L1 research.
- Analysis of PD-1/PD-L1 structure, expression, and signaling.
- Synthesis of current therapeutic approaches and resistance mechanisms.
Main Results:
- PD-1/PD-L1 are key regulators of T-cell function, crucial for immune evasion.
- Anti-PD-1/PD-L1 therapies show efficacy in various cancers but suffer from low response rates and acquired resistance.
- Understanding PD-1/PD-L1 biology is essential for improving therapeutic outcomes.
Conclusions:
- Reactivating anti-tumor immunity via PD-1/PD-L1 blockade offers significant therapeutic potential.
- Overcoming resistance to PD-1/PD-L1 therapies requires further research into underlying mechanisms.
- Future strategies should focus on enhancing patient response and preventing resistance to immunotherapy.
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