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Understanding immune checkpoints and PD-1/PD-L1-mediated immune resistance towards tumour immunotherapy

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Abstract

Immunotherapy has emerged as a transformative approach in the treatment of various cancers, offering new hope for patients previously faced with limited treatment options. A cornerstone of cancer immunotherapy lies in targeting immune checkpoints, particularly the programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway. Immune checkpoints serve as crucial regulators of the immune response, preventing excessive immune activity and maintaining self-tolerance. PD-1, expressed on the surface of T cells, and its ligand PD-L1, expressed on various cell types, including cancer cells and immune cells, play a central role in this regulatory process. Although the success rate associated with these immunotherapies is very promising, most patients still show intrinsic or acquired resistance. Since the mechanisms related to PD-1/PD-L1 resistance are not well understood, an in-depth analysis is necessary to improve the success rate of anti-PD-1/PD-L1 therapy. Hence, here we provide an overview of PD-1, its ligand PD-L1, and the resistance mechanism towards PD-1/PD-L1. Furthermore, we have discussed the plausible solution to increase efficacy and clinical response. For the following research, joint endeavours of clinicians and basic scientists are essential to address the limitation of resistance towards immunotherapy.

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Authors and Affiliations

  1. School of Bioscience and Bioengineering, D Y Patil International University, Pune, Maharastra, 411051, India

    Sidhartha Singh

  2. Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Navneet Singh

  3. Department of Regulatory Affairs, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, 500037, India

    S. S. Kirthiga Devi & Sandeep Kumar

  4. Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, 147004, India

    Manoj Baranwal & Siddharth Sharma

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  1. Sidhartha Singh
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  2. Navneet Singh
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  5. S. S. Kirthiga Devi
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Contributions

Conceptualisation, writing original draft, review, and editing: SS, NS, and MB; data curation and original draft preparation: SS; writing and editing support: KDSS; supervision, formal analysis, and validation: SK.

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Correspondence to Sandeep Kumar.

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Singh, S., Singh, N., Baranwal, M. et al. Understanding immune checkpoints and PD-1/PD-L1-mediated immune resistance towards tumour immunotherapy. 3 Biotech 13, 411 (2023). https://doi.org/10.1007/s13205-023-03826-2

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