Programmed cell death-ligand 2: A neglected but important target in the immune response to cancer?
Cinzia Solinas1, Marco Aiello2, Esdy Rozali3
1Azienda USL Valle d'Aosta, Regional Hospital of Valle d'Aosta, Aosta, Italy.
Abstract:
Programmed cell death-ligand 2 (PD-L2) is one of the two ligands of the programmed cell death-1 (PD-1) receptor, an inhibitory protein mainly expressed on activated immune cells that is targeted in the clinic, with successful and remarkable results. The PD-1/PD-Ls axis was shown to be one of the most relevant immunosuppressive pathways in the immune microenvironment, and blocking this interaction gave rise to an impressive clinical benefit in a broad variety of solid and hematological malignancies. Although PD-L2 has been historically considered a minor ligand, it binds to PD-1 with a two- to six-fold higher affinity as compared to PD-L1. PD-L2 can be expressed by immune, stromal, or tumor cells. The aims of this narrative review are to summarize PD-L2 biology in the physiological responses of the immune system and its role, expression, and clinical significance in cancer.
Insights
Programmed cell death-ligand 2 (PD-L2) binds PD-1 with higher affinity than PD-L1. This review summarizes PD-L2 biology and its crucial role in cancer immunity and treatment.
Area of Science:
- Immunology
- Oncology
Background:
- The programmed cell death-1 (PD-1)/programmed cell death-ligands (PD-Ls) axis is a key immunosuppressive pathway in cancer.
- Blocking the PD-1/PD-Ls interaction yields significant clinical benefits across various malignancies.
Purpose of the Study:
- To review the biological functions of PD-L2 in physiological immune responses.
- To elucidate the role, expression patterns, and clinical significance of PD-L2 in cancer.
Main Methods:
- This is a narrative review.
- Literature search on PD-L2 biology, immune interactions, and cancer applications.
Main Results:
- PD-L2 binds to the PD-1 receptor with 2-6 times higher affinity than PD-L1.
- PD-L2 is expressed by immune, stromal, and tumor cells, influencing the tumor microenvironment.
- Despite being historically underestimated, PD-L2 plays a significant role in immune regulation.
Conclusions:
- PD-L2 is a critical modulator of immune responses with substantial implications in cancer.
- Understanding PD-L2 biology is essential for optimizing cancer immunotherapy strategies.
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