Evidence map›Paper›PMID 36038629›Full record

ArticleNature medicine2022

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma.

Nathalie Scholler, Regis Perbost, Frederick L Locke, Michael D Jain, Sarah Turcan, Corinne Danan, Edmund C Chang, Sattva S Neelapu, David B Miklos, Caron A Jacobson and 12 more

Open access · hybridAbstract read
In one paragraph

Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 1 pooled it
18.4field-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

147 citing papers in PubMed, 1 synthesis or guideline pooled it, 187 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 9 institutions in 2 countries.

Nathalie SchollerKite, a Gilead company, Santa Monica, CA, USA.
Regis PerbostVeracyte SAS, Marseille, France.
Frederick L LockeMoffitt Cancer Center, Tampa, FL, USA.ORCID http://orcid.org/0000-0001-9063-6691
Michael D JainMoffitt Cancer Center, Tampa, FL, USA.ORCID http://orcid.org/0000-0002-7789-1257
Sarah TurcanVeracyte SAS, Marseille, France.
Corinne DananVeracyte SAS, Marseille, France.
Edmund C ChangKite, a Gilead company, Santa Monica, CA, USA.
Sattva S NeelapuThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1045-4914
David B MiklosStanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0717-4305
Caron A JacobsonDana-Farber Cancer Institute, Boston, MA, USA.
Lazaros J LekakisUniversity of Miami Health System, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
Yi LinMayo Clinic, Rochester, MN, USA.
Armin GhobadiWashington University School of Medicine, St. Louis, MO, USA.
Jenny J KimKite, a Gilead company, Santa Monica, CA, USA.
Justin ChouKite, a Gilead company, Santa Monica, CA, USA.
Vicki PlaksKite, a Gilead company, Santa Monica, CA, USA.
Zixing WangKite, a Gilead company, Santa Monica, CA, USA.
Allen XueKite, a Gilead company, Santa Monica, CA, USA.
Mike MattieKite, a Gilead company, Santa Monica, CA, USA.
John M RossiKite, a Gilead company, Santa Monica, CA, USA.
Adrian BotKite, a Gilead company, Santa Monica, CA, USA.
Jérôme GalonVeracyte SAS, Marseille, France. jerome.galon@crc.jussieu.fr.ORCID http://orcid.org/0000-0001-9635-1339
Moffitt Cancer Center · USDana-Farber Cancer Institute · USGilead Sciences (United States) · USInserm · FRMayo Clinic in Arizona · USStanford University · USThe University of Texas MD Anderson Cancer Center · USUniversity of Miami Health System · USWashington University in St. Louis · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell subsets were validated in three independent LBCL datasets. In the ZUMA-1 trial samples, clinical response and overall survival were associated with pre-treatment immune contexture as characterized by Immunoscore and Immunosign 21. Circulating CAR T cell levels were associated with post-treatment TME T cell exhaustion. TME enriched for chemokines (CCL5 and CCL22), γ-chain receptor cytokines (IL-15, IL-7 and IL-21) and interferon-regulated molecules were associated with T cell infiltration and markers of activity. Finally, high density of regulatory T cells in pre-treatment TME associated with reduced axi-cel-related neurologic toxicity. These findings advance the understanding of LBCL TME characteristics associated with clinical responses to anti-CD19 CAR T cell therapy and could foster biomarker development and treatment optimization for patients with LBCL.

Indexed as

Biological ProductsLymphoma, Large B-Cell, DiffuseReceptors, Chimeric AntigenAntigens, CD19Cell CountHumansImmunotherapy, AdoptiveInterferonsInterleukin-15Interleukin-7Tumor MicroenvironmentAntigens, CD19Biological ProductsInterferonsInterleukin-15Interleukin-7Receptors, Chimeric Antigen

Identifiers

PMID36038629
PMCPMC9499856
OpenAlexW4293476190

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.