Evidence map›Paper›PMID 36347876›Full record

ArticleNature communications2022

CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia.

Awatef Allouch, Laurent Voisin, Yanyan Zhang, Syed Qasim Raza, Yann Lecluse, Julien Calvo, Dorothée Selimoglu-Buet, Stéphane de Botton, Fawzia Louache, Françoise Pflumio and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed, 19 citations in OpenAlex.

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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

12 authors at 3 institutions in 2 countries.

Awatef AllouchUniversité Paris-Saclay, Inserm UMR1030, Laboratory of Molecular Radiotherapy and Therapeutic Innovation, Villejuif, F-94805, France. awatef.allouch@gustaveroussy.fr.ORCID 0000-0003-1232-0629
Laurent VoisinUniversité Paris-Saclay, Inserm UMR1030, Laboratory of Molecular Radiotherapy and Therapeutic Innovation, Villejuif, F-94805, France.
Yanyan ZhangGustave Roussy Cancer Center, Villejuif, F-94805, France.
Syed Qasim RazaUniversité Paris-Saclay, Inserm UMR1030, Laboratory of Molecular Radiotherapy and Therapeutic Innovation, Villejuif, F-94805, France.
Yann LecluseGustave Roussy Cancer Center, Villejuif, F-94805, France.
Julien CalvoUniversité de Paris, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, F-92260, France.ORCID 0000-0003-1316-4306
Dorothée Selimoglu-BuetGustave Roussy Cancer Center, Villejuif, F-94805, France.ORCID 0000-0002-3565-2709
Stéphane de BottonGustave Roussy Cancer Center, Villejuif, F-94805, France.
Fawzia LouacheGustave Roussy Cancer Center, Villejuif, F-94805, France.
Françoise PflumioUniversité de Paris, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, F-92260, France.ORCID 0000-0001-8995-596X
Eric SolaryGustave Roussy Cancer Center, Villejuif, F-94805, France.ORCID 0000-0002-8629-1341
Jean-Luc PerfettiniUniversité Paris-Saclay, Inserm UMR1030, Laboratory of Molecular Radiotherapy and Therapeutic Innovation, Villejuif, F-94805, France. jean-luc.perfettini@gustaveroussy.fr.ORCID 0000-0002-2427-2604
Inserm · FRCentre National de la Recherche Scientifique · FRInstitut Gustave Roussy · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) has emerged as a therapeutic opportunity for cancer treatment. Here, we demonstrate that tumor cell phagocytosis drives the pro-inflammatory activation of TAMs and identify a key role for the cyclin-dependent kinase inhibitor CDKN1A (p21). Through the transcriptional repression of Signal-Regularity Protein α (SIRPα), p21 promotes leukemia cell phagocytosis and, subsequently, the pro-inflammatory reprogramming of phagocytic macrophages that extends to surrounding macrophages through Interferon γ. In mouse models of human T-cell acute lymphoblastic leukemia (T-ALL), infusion of human monocytes (Mos) engineered to overexpress p21 (p21TD-Mos) leads to Mo differentiation into phagocytosis-proficient TAMs that, after leukemia cell engulfment, undergo pro-inflammatory activation and trigger the reprogramming of bystander TAMs, reducing the leukemic burden and substantially prolonging survival in mice. These results reveal p21 as a trigger of phagocytosis-guided pro-inflammatory TAM reprogramming and highlight the potential for p21TD-Mo-based cellular therapy as a cancer immunotherapy.

Indexed as

Leukemia, Myeloid, AcutePhagocytosisAnimalsCyclin-Dependent Kinase Inhibitor p21HumansImmunotherapyMacrophagesMiceCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21

Identifiers

PMID36347876
PMCPMC9643439
OpenAlexW4308518802

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.