Evidence map›Paper›PMID 31164357›Full record

ArticleCancer immunology research2019

Inhibition of the NKp44-PCNA Immune Checkpoint Using a mAb to PCNA.

Kiran Kundu, Susmita Ghosh, Rhitajit Sarkar, Avishay Edri, Michael Brusilovsky, Orly Gershoni-Yahalom, Rami Yossef, Avishai Shemesh, Jean-Charles Soria, Vladimir Lazar and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

29 citing papers in PubMed, 34 citations in OpenAlex.

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  6. DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

14 authors at 6 institutions in 4 countries.

Kiran KunduThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Susmita GhoshThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Rhitajit SarkarThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID 0000-0001-7287-0388
Avishay EdriThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Michael BrusilovskyDivision of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Orly Gershoni-YahalomThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Rami YossefSurgery Branch, NCI, NIH, Bethesda, Maryland.
Avishai ShemeshThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Jean-Charles SoriaGustave Roussy, Villejuif, France.
Vladimir LazarWorldwide Innovative Network (WIN) Association - WIN Consortium, Villejuif, France.
Ben-Zion JoshuaDepartment of Otolaryngology-Head and Neck Surgery, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID 0000-0002-2010-892X
Kerry S CampbellInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Moshe ElkabetsThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID 0000-0003-3634-9098
Angel PorgadorThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. angel@bgu.ac.il.
Ben-Gurion University of the Negev · ILCincinnati Children's Hospital Medical Center · USFox Chase Cancer Center · USNational Institutes of Health · USUniversité Paris-Sud · FRWine Australia · AU

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
NCI NIH HHS P30 CA006927
6 · The paper itself

Abstract

mAb-based blocking of the immune checkpoints involving the CTLA4-B7 and PD1-PDL1 inhibitory axes enhance T-cell-based adaptive immune responses in patients with cancer. We show here that antitumor responses by natural killer (NK) cells can be enhanced by a checkpoint-blocking mAb, 14-25-9, which we developed against proliferating cell nuclear antigen (PCNA). PCNA is expressed on the surface of cancer cells and acts as an inhibitory ligand for the NK-cell receptor, NKp44-isoform1. We tested for cytoplasmic- and membrane-associated PCNA by FACS- and ImageStream-based staining of cell lines and IHC of human cancer formalin fixed, paraffin embedded tissues. The mAb, 14-25-9, inhibited binding of chimeric NKp44 receptor to PCNA and mostly stained the cytoplasm and membrane of tumor cells, whereas commercial antibody (clone PC10) stained nuclear PCNA. NK functions were measured using ELISA-based IFNγ secretion assays and FACS-based killing assays. The NK92-NKp44-1 cell line and primary human NK cells showed increased IFNγ release upon coincubation with mAb 14-25-9 and various solid tumor cell lines and leukemias. Treatment with 14-25-9 also increased NK cytotoxic activity.

Indexed as

AnimalsAntibodies, MonoclonalApoptosisCell ProliferationCytotoxicity, ImmunologicHead and Neck NeoplasmsHumansKiller Cells, NaturalMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDNatural Cytotoxicity Triggering Receptor 2Proliferating Cell Nuclear AntigenSquamous Cell Carcinoma of Head and NeckTumor Cells, CulturedAntibodies, MonoclonalNatural Cytotoxicity Triggering Receptor 2NCR2 protein, humanPCNA protein, humanProliferating Cell Nuclear Antigen

Identifiers

PMID31164357
PMCPMC7233522
OpenAlexW2948156543

What OpenQuestion holds

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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.