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Reprogramming the tumor microenvironment to boost adoptive T cell therapy
Maria Fernanda Meza Pacheco1,2, Lee-Hwa Tai1,2
1Departement of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.
Frontiers in Immunology
|November 10, 2025
Summary
Next-generation adoptive T cell therapies (ACT) need to overcome the immunosuppressive tumor microenvironment (TME). Strategies involve reprogramming the TME and integrating ACT with conventional treatments for better solid tumor outcomes.
Area of Science:
- Immunology
- Oncology
- Bioengineering
Background:
- Adoptive T cell therapies (ACT) show promise in hematologic cancers but face challenges in solid tumors.
- The tumor microenvironment (TME) is a significant barrier due to its complexity and immunosuppressive nature.
Purpose of the Study:
- To review emerging strategies for enhancing ACT efficacy in solid tumors.
- To propose an integrated approach focusing on T cell-TME interactions for future ACT development.
Main Methods:
- Comprehensive literature review of TME reprogramming strategies.
- Analysis of emerging therapies and their clinical translation potential.
- Exploration of integrating conventional therapies with ACT.
Main Results:
- Several strategies can enhance ACT efficacy by modifying the TME, including vascular reprogramming, myeloid cell repolarization, oncolytic viruses, sterile inflammation induction, and targeting the extracellular matrix.
- Some novel approaches are progressing to clinical trials.
- Conventional therapies can be strategically combined with ACT.
Conclusions:
- Future ACT success in solid tumors hinges on reprogramming the TME to support T cell function.
- An integrated approach combining T cell engineering with TME modulation is crucial.
- Interdisciplinary collaboration is essential for advancing ACT.
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