4.7 Review

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Journal

FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.731798

Keywords

PD-1 inhibitor; PD-L1 inhibitor; biomarkers; immune checkpoint; tumor immune escape; immune-related toxicity; immunotherapy

Funding

  1. National Nature Science Foundation of China [21775061]
  2. Shandong Provincial Key Research and Development Program [2019GSF108253]
  3. Open Funds of State Key Laboratory of ChemoBiosensing [2019016]
  4. Science Foundation of Innovative Research Teams of Accurate Disease Identification and Targeted Therapy [22202105]

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Programmed death protein 1 (PD1) is an important immune checkpoint on T cells that plays a crucial role in downregulating the immune system and promoting self-tolerance, while its ligand, programmed cell death ligand 1 (PDL1), is overexpressed in malignant tumor cells, contributing to immune evasion and treatment failure. Despite the clinical efficacy of PD1/PDL1 inhibitors in many tumors, some patients may develop drug resistance, highlighting the need for further research into improving targeted therapies and understanding the associated safety issues.
Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.

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