Evidence map›Paper›PMID 41997129›Full record

ReviewCell2026

Mapping intratumor heterogeneity across layers for advancing immunotherapy.

Jean-Christophe Marine, Osnat Bartok, Shira Sagie, Pietro Paolo Vitiello, Alberto Bardelli, Chen Weller, Tian-Gen Chang, Claudia Tonelli, Stefani Spranger, Eytan Ruppin and 1 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

11 authors.

Jean-Christophe MarineLaboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KULeuven, Leuven, Belgium.
Osnat BartokDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shira SagieDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Jusidman Cancer Center, Sheba Medical Center, 52621 Ramat Gan, Israel.
Pietro Paolo VitielloDepartment of Oncology, Molecular Biotechnology Center, University of Torino, 10126 Turin, Italy; IFOM ETS, The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Alberto BardelliDepartment of Oncology, Molecular Biotechnology Center, University of Torino, 10126 Turin, Italy; IFOM ETS, The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Chen WellerDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Tian-Gen ChangCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Claudia TonelliLaboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KULeuven, Leuven, Belgium.
Stefani SprangerKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA; Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
Eytan RuppinCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Translational Research Institute, The Jim and Eleanor Randall Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yardena SamuelsDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: yardena.samuels@weizmann.ac.il.

Funding

Mutational and Functional Analysis of Sporadic Malignant MelanomaZIAHG200337 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SAMUELS, YARDENA · 2009 to 2013
$5.0M
Mutational analysis of signal transducing gene families in malignant melanomaZ01HG200337 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SAMUELS, YARDENA · 2007 to 2008
$3.5M
Intramural NIH HHS Z01 HG200337Intramural NIH HHS ZIA HG200337
6 · The paper itself

Abstract

Intratumor heterogeneity (ITH) encompasses genetic, epigenetic, transcriptional, proteomic, and immunopeptidomic diversity. Beyond genetic heterogeneity, it is increasingly clear that non-mutational heterogeneity and plasticity generate dynamic cancer cell states with distinct immune visibility. These layers of complexity converge on the immunopeptidome, the repertoire of peptides displayed by major histocompatibility complex molecules through which tumor cells are surveyed by T cells. Variation in antigen processing, presentation, and peptide abundance across cancer clones and cell states yields spatially and temporally distinct immunological niches that shape immune recognition and therapeutic response. Here, we summarize how multidimensional ITH manifests across cancer types and constrains immunotherapy efficacy. We propose that integrating measurements across layers is a promising direction for improving biomarker identification and informing more precise immune-based treatment strategies.

Indexed as

Genetic HeterogeneityImmunotherapyNeoplasmsAnimalsHumansProteomicsT-Lymphocytes

Identifiers

PMID41997129
PMCPMC13283290

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.