Evidence map›Paper›PMID 39272096›Full record

Trial reportMolecular cancer2024

Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics.

Sophie Cousin, Jean-Philippe Guégan, Kohei Shitara, Lola Jade Palmieri, Jean Philippe Metges, Simon Pernot, Shota Fukuoka, Shohei Koyama, Hiroyoshi Nishikawa, Carine A Bellera and 10 more

Abstract readClinical Trial, Phase IILetterMulticenter Study
In one paragraph

Trial report in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–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

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  15. Overcoming resistance to anti-PD-1/PD-L1 therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2026
    Review
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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

20 authors.

Sophie Cousin *Department of Medicine, Institut Bergonié, 229 cours de l'Argonne, Bordeaux, 33000, France.
Jean-Philippe Guégan *Explicyte, Bordeaux, France.
Kohei ShitaraDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan.
Lola Jade PalmieriDepartment of Medicine, Institut Bergonié, 229 cours de l'Argonne, Bordeaux, 33000, France.
Jean Philippe MetgesDepartment of Oncology, University Hospital Center of Brest, Brest, France.
Simon PernotDepartment of Medicine, Institut Bergonié, 229 cours de l'Argonne, Bordeaux, 33000, France.
Shota FukuokaDivision of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Chiba, 104-0045, 277-8577, Japan.
Shohei KoyamaDivision of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Chiba, 104-0045, 277-8577, Japan.
Hiroyoshi NishikawaDivision of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Chiba, 104-0045, 277-8577, Japan.
Carine A BelleraBordeaux Population Health Research Center, Univ. Bordeaux, Epicene team, UMR 1219, Inserm, Bordeaux, France.
Antoine AdenisDepartment of Medicine, Institut Cancerologie Montpellier, Montpellier, France.
Carlos A Gomez-RocaDepartment of Medicine, Oncopole, Toulouse, France.
Philippe Alexandre CassierDepartment of Medicine, Centre Leon Bérard, Lyon, France.
Antoine HollebecqueDITEP, Gustave Roussy, Villejuif, France.
Coralie CantarelBordeaux Population Health Research Center, Univ. Bordeaux, Epicene team, UMR 1219, Inserm, Bordeaux, France.
Michèle KindDepartment of Radiology, Institut Bergonié, Bordeaux, France.
Isabelle SoubeyranDepartment of Pathology, Institut Bertognié, Bordeaux, France.
Lucile VanherseckeDepartment of Pathology, Institut Bertognié, Bordeaux, France.
Alban BessedeExplicyte, Bordeaux, France.
Antoine ItalianoDepartment of Medicine, Institut Bergonié, 229 cours de l'Argonne, Bordeaux, 33000, France. a.italiano@bordeaux.unicancer.fr.

Funding

Association pour la recherche contre le cancer REGOMUNEBayer REGOMUNE
6 · The paper itself

Abstract

Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. This therapeutic regimen resulted in deep and durable responses in 19% of patients, with the median duration of response not yet reached. Notwithstanding, a significant proportion of AGC patients exhibited no therapeutic advantage, prompting investigations into mechanisms of inherent resistance. Comprehensive biomarker profiling elucidated that non-responders predominantly exhibited an augmented presence of M2 macrophages within the tumor microenvironment and a marked overexpression of S100A10 by neoplastic cells, a protein previously implicated in macrophage chemotaxis. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.

Indexed as

B7-H1 AntigenDrug Resistance, NeoplasmProteomicsStomach NeoplasmsTumor MicroenvironmentAngiogenesis InhibitorsBiomarkers, TumorFemaleGene Expression ProfilingHumansImmune Checkpoint InhibitorsMaleMiddle AgedProgrammed Cell Death 1 ReceptorTranscriptomeAngiogenesis InhibitorsB7-H1 AntigenBiomarkers, TumorCD274 protein, humanImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID39272096
PMCPMC11396962

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.