Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28: British Journal of Pharmacology

F.R. Mariotti, L. Quatrini, E. Munari, P. Vacca, N. Tumino, G. Pietra, M.C. Mingari, L. Moretta

Research output: Contribution to journalArticlepeer-review


Immune checkpoint inhibitors have revolutionized cancer therapy leading to exceptional success. However, there is still the need to improve their efficacy in non-responder patients. Natural killer (NK) cells represent the first line of defence against tumours, due to their ability to release immunomodulatory cytokines and kill target cells that have undergone malignant transformation. Harnessing NK cell response will open new possibilities to improve control of tumour growth. In this respect inhibitory checkpoints expressed on these innate lymphocytes represents a promising target for next-generation immunotherapy. In this review, we will summarize recent evidences on the expression of NK cells receptors in cancer, with a focus on the inhibitory checkpoint programmed cell death protein 1 (PD-1). We will also highlight the strength and limitations of the blockade of PD-1 inhibitory pathway and suggest new combination strategies that may help to unleash more efficiently NK cell anti-tumour response. © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society
Original languageEnglish
Pages (from-to)2889-2903
Number of pages15
JournalBr. J. Pharmacol.
Issue number13
Publication statusPublished - 2020


  • antineoplastic monoclonal antibody
  • atezolizumab
  • avelumab
  • cytotoxic T lymphocyte antigen 4
  • durvalumab
  • ecalectin
  • hepatitis A virus cellular receptor 2
  • HLA antigen class 1
  • indoleamine 2,3 dioxygenase
  • ipilimumab
  • killer cell immunoglobulin like receptor
  • killer cell immunoglobulin like receptor 2DL4
  • leukocyte immunoglobulin like receptor subfamily B member 1
  • monalizumab
  • natural killer cell receptor
  • natural killer cell receptor NKG2D
  • nivolumab
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  • programmed death 1 ligand 1
  • programmed death 1 ligand 2
  • programmed death 1 receptor
  • properdin
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  • antineoplastic activity
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  • enzyme activation
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  • gastrointestinal carcinoma
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  • human
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  • malignant neoplasm
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  • natural killer cell
  • non small cell lung cancer
  • nonhuman
  • priority journal
  • protein expression
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