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The Immune Checkpoint PD-1 in Natural Killer Cells: Expression, Function and Targeting in Tumour Immunotherapy

Linda Quatrini1, Francesca Romana Mariotti1, Enrico Munari2

  • 1Department of Immunology, IRCCS Bambino Gesù Children's Hospital, 00146 Rome, Italy.

Cancers
|November 11, 2020
PubMed

Insights

Immunotherapy targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1) revolutionizes cancer treatment by enhancing T cell responses. Recent findings highlight PD-1

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immunotherapy using antibodies against programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) has transformed cancer treatment.
  • Initial understanding attributed efficacy solely to T cell activation.
  • Emerging evidence shows PD-1 expression and function in Natural Killer (NK) cells, suggesting broader immune involvement.

Purpose of the Study:

  • To review the role of PD-1 in NK cell function within the context of anti-PD-1/PD-L1 immunotherapy.
  • To explore the implications of PD-1/PD-L1 blockade on NK cell-mediated anti-tumour responses.
  • To discuss current limitations and future perspectives for checkpoint inhibitor therapies.

Main Methods:

  • Literature review of studies investigating PD-1 expression and function in NK cells.
  • Analysis of existing data on PD-1/PD-L1 blockade efficacy in various tumour types.
  • Synthesis of findings related to NK cell responses to immunotherapy.

Main Results:

  • PD-1 is expressed on NK cells and influences their anti-tumour activity.
  • Anti-PD-1/PD-L1 therapies can potentially restore or enhance NK cell anti-tumour functions.
  • Tumour responsiveness to PD-1/PD-L1 blockade is observed even in cancers with low Human Leukocyte Antigen (HLA) I expression, suggesting NK cell involvement.

Conclusions:

  • The contribution of NK cells to the efficacy of anti-PD-1/PD-L1 therapy is increasingly recognized.
  • A deeper understanding of checkpoint molecule biology in NK cells is crucial.
  • This knowledge will inform the development of improved immunotherapeutic strategies and clinical protocols.
Keywords:
NK cellsPD-1PD-L1glucocorticoidsimmunotherapyinhibitory checkpointssoluble PD-1tumour microenvironment

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