Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy

Abstract Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programme...

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Main Authors: Yogesh Godiyal, Drishti Maheshwari, Hiroaki Taniguchi, Shweta S. Zinzuwadia, Yanelys Morera-Díaz, Devesh Tewari, Anupam Bishayee
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Military Medical Research
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Online Access:https://doi.org/10.1186/s40779-024-00586-9
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author Yogesh Godiyal
Drishti Maheshwari
Hiroaki Taniguchi
Shweta S. Zinzuwadia
Yanelys Morera-Díaz
Devesh Tewari
Anupam Bishayee
author_facet Yogesh Godiyal
Drishti Maheshwari
Hiroaki Taniguchi
Shweta S. Zinzuwadia
Yanelys Morera-Díaz
Devesh Tewari
Anupam Bishayee
author_sort Yogesh Godiyal
collection DOAJ
description Abstract Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1). The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system. Furthermore, it controls the phenotype and functionality of innate and adaptive immune components. A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints. This could contribute to the existing arsenal of anticancer drugs. Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis, promoting tumor cell apoptosis, influencing cell proliferation, and eventually leading to tumor cell death and inhibiting cancer progression. However, there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer. Hence, this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
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spelling doaj-art-9b9837857af1462db2fa571f326cfa7a2025-08-20T02:32:01ZengBMCMilitary Medical Research2054-93692024-12-0111115110.1186/s40779-024-00586-9Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapyYogesh Godiyal0Drishti Maheshwari1Hiroaki Taniguchi2Shweta S. Zinzuwadia3Yanelys Morera-Díaz4Devesh Tewari5Anupam Bishayee6Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research UniversityDepartment of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research UniversityDepartment of Experimental Embryology, Institute of Genetics and Animal Biotechnology of the Polish Academy of SciencesDepartment of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic MedicineClinical Investigation and Biomedical Research Directions, Center for Genetic Engineering and BiotechnologyDepartment of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research UniversityDepartment of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic MedicineAbstract Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1). The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system. Furthermore, it controls the phenotype and functionality of innate and adaptive immune components. A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints. This could contribute to the existing arsenal of anticancer drugs. Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis, promoting tumor cell apoptosis, influencing cell proliferation, and eventually leading to tumor cell death and inhibiting cancer progression. However, there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer. Hence, this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.https://doi.org/10.1186/s40779-024-00586-9CancerPD-1/PD-L1CrosstalkNatural compoundsTherapeutic targets
spellingShingle Yogesh Godiyal
Drishti Maheshwari
Hiroaki Taniguchi
Shweta S. Zinzuwadia
Yanelys Morera-Díaz
Devesh Tewari
Anupam Bishayee
Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
Military Medical Research
Cancer
PD-1/PD-L1
Crosstalk
Natural compounds
Therapeutic targets
title Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
title_full Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
title_fullStr Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
title_full_unstemmed Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
title_short Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
title_sort role of pd 1 pd l1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
topic Cancer
PD-1/PD-L1
Crosstalk
Natural compounds
Therapeutic targets
url https://doi.org/10.1186/s40779-024-00586-9
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