Evidence map›Paper›PMID 41422061›Full record

ArticleNature communications2025

Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors.

Vignesh Shanmugam, Neriman Tokcan, Daniel Chafamo, Sean Sullivan, Mehdi Borji, Haley Martin, Gail Newton, Naeem Nadaf, Saoirse Hanbury, Irving Barrera and 11 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Review
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  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Vignesh Shanmugam *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Neriman Tokcan *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel ChafamoKlarman Cell Observatory, Broad Institute, Cambridge, MA, USA.ORCID http://orcid.org/0009-0001-8877-5913
Sean SullivanBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0001-0435-2957
Mehdi BorjiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Haley MartinDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Gail NewtonDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Naeem NadafBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7805-8523
Saoirse HanburyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Irving BarreraBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Dylan CableBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jackson WeirBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8741-1344
Orr AshenbergKlarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
Geraldine PinkusDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Scott RodigDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1761-9769
Caroline UhlerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Evan MacoskoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2794-5165
Margaret ShippBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3949-6897
Abner LouissaintBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Fei ChenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2308-3649
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, MA, USA. golub@broadinstitute.org.ORCID http://orcid.org/0000-0003-0113-2403

Funding

Making cancer precision medicine real: bottlenecks and opportunitiesR35CA242457 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2019 to 2025
$6.9M
NCI NIH HHS R35 CA242457U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R35CA242457
6 · The paper itself

Abstract

A central challenge in cancer research is to identify the secreted factors that sustain tumor cell survival. This is best exemplified in Hodgkin lymphoma, where malignant cells constitute a minor fraction of the tumor and rely on signals from the microenvironment for survival. Using genome-wide transcriptional profiling with spatial and single-cell resolution, we show that the neighborhood around malignant cells forms a distinct niche of 31 non-malignant cell types, enriched in helper T cells and myeloid cells, but depleted of plasma cells. Moreover, our spatial analysis nominates IL13 as a candidate survival factor. Recombinant IL13 augments malignant cell growth in vitro, and genome-wide loss-of-function screens across >1000 human cancer cell lines identify IL4R and IL13RA1, heterodimeric components of the IL13 receptor, as uniquely essential in Hodgkin lymphoma. Importantly, blocking antibodies phenocopy genetic inactivation. Our findings provide a biological rationale for testing IL13-directed therapies, which are already FDA-approved, in Hodgkin lymphoma.

Indexed as

Hodgkin DiseaseTumor MicroenvironmentCell Line, TumorCell SurvivalGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInterleukin-13Interleukin-4 Receptor alpha SubunitSingle-Cell AnalysisIL4R protein, humanInterleukin-13Interleukin-4 Receptor alpha Subunit

Identifiers

PMID41422061
PMCPMC12827949

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.