Evidence map›Paper›PMID 33173077›Full record

ArticleScientific reports2020

Expanded and activated allogeneic NK cells are cytotoxic against B-chronic lymphocytic leukemia (B-CLL) cells with sporadic cases of resistance.

Tania Calvo, Chantal Reina-Ortiz, David Giraldos, María Gascón, Daniel Woods, Judit Asenjo, Joaquín Marco-Brualla, Gemma Azaceta, Isabel Izquierdo, Luis Palomera and 6 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Generation of non-genetically modified, CAR-like, NK cells.Journal for immunotherapy of cancer · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Advances in NK cell production.Cellular & molecular immunology · 2022
    Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Natural adjuvants (Gastroenterology and hepatology from bed to bench · 2022
    Article
  20. Review
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

16 authors at 7 institutions in 2 countries.

Tania CalvoApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Chantal Reina-OrtizApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
David GiraldosApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
María GascónApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Daniel WoodsApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Judit AsenjoImmunogenetics-HLA Laboratory, Puerta de Hierro Hospital, Majadahonda, Madrid, Spain.
Joaquín Marco-BruallaApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Gemma AzacetaHematology Department, Lozano Blesa Hospital, Zaragoza, Spain.
Isabel IzquierdoHematology Department, Miguel Servet Hospital, Zaragoza, Spain.
Luis PalomeraHematology Department, Lozano Blesa Hospital, Zaragoza, Spain.
Diego Sánchez-MartínezIRMB, Univ Montpellier, INSERM, CNRS, Montpellier, France.
Isabel MarzoApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Javier NavalApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Carlos VilchesImmunogenetics-HLA Laboratory, Puerta de Hierro Hospital, Majadahonda, Madrid, Spain.
Martín VillalbaIRMB, Univ Montpellier, INSERM, CNRS, Montpellier, France.
Alberto AnelApoptosis, Immunity & Cancer Group, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain. anel@unizar.es.
Universidad de Zaragoza · ESHospital Clínico Universitario Lozano Blesa · ESHospital Universitario Puerta de Hierro Majadahonda · ESInstituto de Investigación Sanitaria Aragón · ESCentre National de la Recherche Scientifique · FRHospital Universitario Miguel Servet · ESInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B-CLL patients, with only 1 sample exhibiting resistance. This sporadic resistance did not correlate with match between KIR ligands expressed by the eNK cells and the leukemic cells, while cells with match resulted sensitive to eNK cells. This suggests that KIR mismatch is not relevant when expanded NK cells are used as effectors. In addition, we found two examples of de novo resistance to eNK cell cytotoxicity during the clinical course of the disease. Resistance correlated with KIR-ligand match in one of the patients, but not in the other, and was associated with a significant increase in PD-L1 expression in the cells from both patients. Treatment of one of these patients with idelalisib correlated with the loss of PD-L1 expression and with re-sensitization to eNK cytotoxicity. We confirmed the idelalisib-induced decrease in PD-L1 expression in the B-CLL cell line Mec1 and in cultured cells from B-CLL patients. As a main conclusion, our results reinforce the feasibility of using expanded and activated allogeneic NK cells in the treatment of B-CLL.

Indexed as

Antineoplastic AgentsB7-H1 AntigenCell Line, TumorCells, CulturedCytotoxicity, ImmunologicFlow CytometryHumansImmunotherapy, AdoptiveKiller Cells, NaturalLeukemia, Lymphocytic, Chronic, B-CellAntineoplastic AgentsB7-H1 Antigen

Identifiers

PMID33173077
PMCPMC7655821
OpenAlexW3104002674

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.