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iScience

iScience

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Tracing specificity of immune landscape remodeling associated with distinct anticancer treatments

Published:20 February 2025 DOI: 10.1016/j.isci.2025.112071 PMID: 40124507
Floriane Cannet,?Célia Sequera,?Paula Michea Veloso,?Abdessamad El Kaoutari,?Melissa Methia,?Sylvie Richelme,?Muge Kaya,?Afef Cherni,?Mathieu Dupont,?Jean-Paul Borg,?Christian Morel,?Yannick Boursier,?Flavio Maina

Abstract

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 Alb-R26 Met "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 Alb-R26 Met 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.

Substances (20)

Materials
Procduct Name CAS Molecular Formula Supplier Price
5-Aza-2'-deoxycytidine 2353-33-5 C8H12N4O4 728 suppliers $8.00-$2480.00
5-Aza-2'-deoxycytidine 2353-33-5 C8H12N4O4 728 suppliers $8.00-$2480.00
5-Aza-2'-deoxycytidine 2353-33-5 C8H12N4O4 728 suppliers $8.00-$2480.00
5-Aza-2'-deoxycytidine 2353-33-5 C8H12N4O4 728 suppliers $8.00-$2480.00
Trametinib 871700-17-3 C26H23FIN5O4 381 suppliers $28.00-$4391.10
Trametinib 871700-17-3 C26H23FIN5O4 381 suppliers $28.00-$4391.10
Trametinib 871700-17-3 C26H23FIN5O4 381 suppliers $28.00-$4391.10
Trametinib 871700-17-3 C26H23FIN5O4 381 suppliers $28.00-$4391.10
ABT 737 852808-04-9 C42H45ClN6O5S2 221 suppliers $27.00-$2822.00
ABT 737 852808-04-9 C42H45ClN6O5S2 221 suppliers $27.00-$2822.00

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