Evidence map›Paper›PMID 40779497›Full record

ArticlePloS one2025

Precision-cut tumor tissue slices, a novel tool to study the tumor microenvironment interactions with chimeric antigen receptor (CAR) T cells.

Valeria Durante, Alina Wittwer, Benjamin Theek, Manuel Martinez-Osuna, Emmanuel Donnadieu, Olaf Hardt, Dominik Eckardt, Andreas Bosio, Sonja Schallenberg, Christoph Herbel

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

10 authors.

Valeria DuranteResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.ORCID https://orcid.org/0009-0009-3293-2607
Alina WittwerResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Benjamin TheekResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Manuel Martinez-OsunaResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Emmanuel DonnadieuUniversité Paris Cité, CNRS, Inserm, Institut Cochin, Equipe Labellisée Ligue Contre le Cancer, Paris, France.
Olaf HardtResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Dominik EckardtResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Andreas BosioResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.ORCID https://orcid.org/0000-0001-9776-2535
Sonja SchallenbergResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.ORCID https://orcid.org/0000-0002-5040-6426
Christoph HerbelResearch and Development Department, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.ORCID https://orcid.org/0000-0002-1933-3070

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Up until present day, chimeric antigen receptor (CAR)-T cell therapy has only been approved for hematological malignancies, as CAR-T cells do not show comparable efficacy in solid tumors. Therefore, understanding the features of the tumor microenvironment (TME), is key to improve efficacy of adoptive cell therapies (ACTs) against solid tumors. In this context, robust workflows, which dissect the complex interactions between CAR-T cells and the TME are still lacking. To address this need, we have established an ex vivo workflow co-culturing tissue slices from patient tumor resections with CAR-T cells. The workflow is composed of assessing several complementary attributes, such as cytokine release via flow cytometry, quantification of cell infiltration into the tumor and assessment of the regions of the tissue slice the CAR-T cell infiltrate into by using the MACSima™ imaging cyclic staining technology. Using this workflow it is possible to observe the behavior of CAR-T cells within the tumor and its TME, their infiltration into distinct tumor compartments, as well as to dissect the underlying molecular mechanisms that drive T cell migration, thanks to MACSima™ multiplexing technology and its ability to image several markers at the same time. Assessment of ovarian carcinoma tissue slices revealed substantial release of specific cytokines and increased infiltration of T cells in the tumor areas when CAR-T cells were added to the tissue slices as compared to non-engineered T cells. The establishment of this novel approach will enable researchers to better characterize the interaction between CAR-T cells and the TME. Tissue slices present an intrinsic heterogeneity, which is indeed an advantage compared to other in vitro models but can turn itself into complex results interpretation. Therefore, we recommend that any conclusion derived from this assay should be verified with complementary models.

Indexed as

Ovarian NeoplasmsReceptors, Chimeric AntigenT-LymphocytesTumor MicroenvironmentCoculture TechniquesCytokinesFemaleFlow CytometryHumansImmunotherapy, AdoptiveCytokinesReceptors, Chimeric Antigen

Identifiers

PMID40779497
PMCPMC12334022

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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.