Evidence map›Paper›PMID 31214193›Full record

ReviewFrontiers in immunology2019

PD/1-PD-Ls Checkpoint: Insight on the Potential Role of NK Cells.

Silvia Pesce, Marco Greppi, Francesco Grossi, Genny Del Zotto, Lorenzo Moretta, Simona Sivori, Carlo Genova, Emanuela Marcenaro

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 182 citations in OpenAlex.

  1. Trial
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  5. Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Integrative genomics and functional immunology reveal Clostridia species as modulators of neuroinflammation in amyotrophic lateral sclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  15. PD-1Journal of experimental & clinical cancer research : CR · 2025
    Article
  16. Article
  17. Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.International journal of molecular sciences · 2025
    Review
  18. Article
  19. NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025
    Review
  20. Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025
    Review

67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Silvia PesceDepartment of Experimental Medicine, University of Genoa, Genoa, Italy.
Marco GreppiDepartment of Experimental Medicine, University of Genoa, Genoa, Italy.
Francesco GrossiMedical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Genny Del ZottoIRCCS, Istituto Giannina Gaslini, Genoa, Italy.
Lorenzo MorettaImmunology Unit, IRCCS Ospedale Bambino Gesù, Rome, Italy.
Simona SivoriDepartment of Experimental Medicine, University of Genoa, Genoa, Italy.
Carlo GenovaLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Emanuela MarcenaroDepartment of Experimental Medicine, University of Genoa, Genoa, Italy.
University of Genoa · ITBambino Gesù Children's Hospital · ITFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITIstituto Giannina Gaslini · ITOspedale Policlinico San Martino · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The identification of inhibitory NK cell receptors specific for HLA-I molecules (KIRs and NKG2A) provided the molecular basis for clarifying the mechanism by which NK cells kill transformed cells while sparing normal cells. The direct interactions between inhibitory NK cell receptors and their HLA-I ligands enable NK cells to distinguish healthy from transformed cells, which frequently show an altered expression of HLA-I molecules. Indeed, NK cells can kill cancer cells that have lost, or under express, HLA-I molecules, but not cells maintaining their expression. In this last case, it is possible to use anti-KIR or anti-NKG2A monoclonal antibodies to block the inhibitory signals generated by these receptors and to restore the anti-tumor NK cell activity. These treatments fall within the context of the new immunotherapeutic strategies known as "immune checkpoint blockade." These antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. However, a more complex scenario has recently emerged. For example, NK cells can also express additional immune checkpoints, including PD-1, that was originally described on T lymphocytes, and whose ligands (PD-Ls) are usually overexpressed on tumor cells. Thus, it appears that the activation of NK cells and their potentially harmful effector functions are under the control of different immune checkpoints and their simultaneous expression could provide additional levels of suppression to anti-tumor NK cell responses. This review is focused on PD-1 immune checkpoint in NK cells, its potential role in immunosuppression, and the therapeutic strategies to recover NK cell cytotoxicity and anti-tumor effect.

Indexed as

AnimalsB7 AntigensB7-H1 AntigenHumansImmunomodulationImmunophenotypingKiller Cells, NaturalLymphocyte ActivationModels, BiologicalProgrammed Cell Death 1 ReceptorT-Lymphocyte SubsetsB7 AntigensB7-H1 AntigenPDCD1 protein, humanProgrammed Cell Death 1 Receptorimmune checkpointimmune checkpoint blockadeimmunotherapyKIRNK cellsNKG2APD-1PD-L

Identifiers

PMID31214193
PMCPMC6557993
OpenAlexW2948843630

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.