Tracing specificity of immune landscape remodeling associated with distinct anticancer treatments
Immune cells within the tumor microenvironment impact cancer progression, resistance, response to treatments. Despite remarkable outcomes for some cancer patients, immunotherapies remain unsatisfactory for others. Here, we designed an experimental setting using the <i>Alb-R26</i> <sup><i>Met</i></sup> "inside-out" mouse model, faithfully recapitulating molecular features of liver cancer patients, to explore the effects of distinct anticancer targeted therapies on the tumor immune landscape. Using two treatments in clinical trials for different cancer types, Decitabine and MEK+BCL-XL blockage, we show their capability to trigger tumor regression in <i>Alb-R26</i> <sup><i>Met</i></sup> mice and to superimpose distinct profiles of immune cell types and immune-checkpoints, impacting immunotherapy response. A machine learning approach processing tumor imaging and immune profile data identified a putative signature predicting tumor treatment response in mice and patients. Outcomes exemplify how the tumor immune microenvironment is differentially reshaped by distinct anticancer agents and highlight the importance of measuring its modulation during treatment to optimize oncotherapy and immunotherapy combinations.
Authors
- Paulo A. S. Veloso
- Jean‐Paul Borg (ORCID: https://orcid.org/0000-0001-8418-3382)
- Célia Sequera
- C. Morel (ORCID: https://orcid.org/0000-0001-5359-6504)
- Sylvie Richelme
- Yannick Boursier (ORCID: https://orcid.org/0000-0003-3235-5271)
- Mehmet Fatih Kaya (ORCID: https://orcid.org/0000-0002-2444-0583)
- Afef Cherni (ORCID: https://orcid.org/0000-0001-5227-6920)
- Flavio Maina (ORCID: https://orcid.org/0000-0001-6100-4695)
- Abdessamad El Kaoutari (ORCID: https://orcid.org/0000-0003-2334-3121)
- Mathieu Dupont (ORCID: https://orcid.org/0000-0001-5228-5608)
- Floriane Cannet
- Melissa Methia
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Universitaire de France (FR)
- Aix-Marseille Université (FR)
- Institut de Biologie du Développement Marseille (FR)
- Centre de Recherche en Cancérologie de Marseille (FR)
- Living Systems (United States) (US)
Publication Details
- Journal
- iScience
- Published
- 2025-02-20
- DOI
- https://doi.org/10.1016/j.isci.2025.112071
- Citations
- 2
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Association pour la Recherche sur le Cancer
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Fondation de France
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Association Française pour l'Etude du Foie
- Canceropôle Provence-Alpes-Côte d’Azur
- Groupement des Entreprises Françaises dans la lutte contre le Cancer
- Société d'Accélération du Transfert de Technologies