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09:04
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in
Xu Wang1, Cuiwei Liu2,3,4,5, Zihan Xia6,7
1The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Cancer Science
|May 7, 2026
Summary
Losartan enhances radiotherapy for triple-negative breast cancer (TNBC) by reversing immune suppression. This novel approach boosts CD8+ T cell activity, offering a promising new treatment strategy for TNBC.
Area of Science:
- Oncology
- Immunology
- Radiotherapy
Background:
- Triple-negative breast cancer (TNBC) is aggressive with limited treatments.
- Radiotherapy (RT) can have dual effects on the tumor microenvironment (TME), potentially causing immunosuppression and radioresistance.
- The renin-angiotensin system (RAS) contributes to immunosuppression and radioresistance in TNBC.
Purpose of the Study:
- To investigate the role of losartan, an angiotensin II receptor blocker (AGTR1), in enhancing TNBC radiosensitivity.
- To explore the immune-dependent mechanisms by which losartan sensitizes TNBC to RT.
- To evaluate losartan's potential to reverse RT-induced immunosuppression in the TME.
Main Methods:
- Analysis of AGTR1 levels in TNBC and correlation with prognosis and radioresistance.
- In vitro and in vivo experiments assessing losartan's effect on TNBC radiosensitivity.
- Immunohistochemical analysis of immune cell populations (TAMs, MDSCs, CD8+ T cells).
- RNA sequencing (RNA-seq) to analyze gene expression changes induced by losartan and RT.
Main Results:
- High AGTR1 levels correlate with poor prognosis and radioresistance in TNBC.
- Losartan significantly enhances TNBC radiosensitivity through immune-dependent mechanisms.
- Losartan inhibits M2 polarization of tumor-associated macrophages (TAMs) and myeloid-derived suppressive cells (MDSCs).
- Losartan upregulates the number and function of tumor-infiltrating CD8+ T lymphocytes.
- Losartan impedes JAK2/STAT1 signaling, reduces interferon-related DNA damage resistance signature (IRDS) expression, and diminishes PD-L1 and IDO in irradiated TNBC cells.
Conclusions:
- Losartan reverses the immunosuppressive TME induced by RT in TNBC.
- Losartan demonstrates potential as an immune-sensitizing agent to improve RT efficacy in TNBC.
- Combination therapy with losartan and RT represents a promising strategy for TNBC treatment.
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