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The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology
Sandra Schöniger1, Bharat Jasani1
1Discovery Life Sciences Biomarker Services GmbH, Germaniastrasse 7, 34119 Kassel, Germany.
Abstract:
The programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway mainly attracted attention in immuno-oncology, leading to the development of immune checkpoint therapy. It has, however, much broader importance for tissue physiology and pathology. It mediates basic processes of immune tolerance and tissue homeostasis. In addition, it is involved in the pathogenesis of chronic infectious diseases, autoimmunity, and cancer. It is also an important paradigm for comparative pathology as well as the "one health one medicine" concept. The aim of this review is to provide an overview of novel research into the diverse facets of the PD-1/PD-L1 pathway and to give insights into its fine-tuning homeostatic role in a tissue-specific context. This review details early translational research from the discovery phase based on mice as animal models for understanding pathophysiological aspects in human tissues to more recent research extending the investigations to several animal species. The latter has the twofold goal of comparing this pathway between humans and different animal species and translating diagnostic tools and treatment options established for the use in human beings to animals and vice versa.
Insights
The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway is crucial for immune tolerance and tissue homeostasis beyond cancer. Research explores its broad physiological roles and comparative pathology across species.
Area of Science:
- Immunology
- Pathology
- Comparative Medicine
Background:
- The PD-1/PD-L1 pathway, known for its role in immuno-oncology and immune checkpoint therapy, also governs fundamental tissue physiology and homeostasis.
- This pathway is implicated in the pathogenesis of chronic infections, autoimmune diseases, and cancer.
- It serves as a key model for comparative pathology and the "one health one medicine" concept.
Purpose of the Study:
- To review novel research on the multifaceted PD-1/PD-L1 pathway.
- To elucidate its homeostatic role in a tissue-specific context.
- To explore translational research from mouse models to diverse animal species.
Main Methods:
- Review of early translational research using mouse models.
- Analysis of recent studies investigating the PD-1/PD-L1 pathway in multiple animal species.
- Comparative analysis of the pathway across species.
Main Results:
- The PD-1/PD-L1 pathway mediates essential immune tolerance and tissue homeostasis.
- Research extends beyond oncology to chronic infectious diseases, autoimmunity, and general pathology.
- Comparative studies reveal conserved and divergent roles of the PD-1/PD-L1 pathway across species.
Conclusions:
- The PD-1/PD-L1 pathway has broad physiological and pathological significance.
- Understanding its tissue-specific homeostatic functions is critical.
- Comparative pathology and One Health approaches are vital for translating findings between humans and animals.
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