2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03J.05 Enhancement of Chemotherapy and Immunotherapy in LUSC Animal Models Through Tumor Microenvironment Remodeling by Losartan

P3.03J.05 Enhancement of Chemotherapy and Immunotherapy in LUSC Animal Models Through Tumor Microenvironment Remodeling by Losartan

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The study explores Losartan, an angiotensin receptor blocker (ARB), and its potential to enhance chemotherapy and immunotherapy for Lung Squamous Cell Carcinoma (LUSC) by remodeling the tumor microenvironment. Angiotensin Receptor Type 1 (AGTR1) expression has been linked to processes such as Epithelial-Mesenchymal Transition (EMT) and immune pathways in LUSC. The study aims to investigate the therapeutic implications of Losartan through animal models.<br /><br />Methods involved using zebrafish and mouse models to assess Losartan’s efficacy in combination with chemotherapy and immunotherapy. Key findings include:<br /><br />1. **Zebrafish Models**: Losartan treatment reduced intra-tumor angiogenesis and tumor cell escape.<br /><br />2. **BALB/C Nude Mouse Models**: The combination of Losartan and cisplatin significantly inhibited LUSC growth compared to cisplatin alone.<br /><br />3. **DBA/2 Mouse Models**: Losartan, combined with cisplatin and PD-1 antibody, was more effective in suppressing LUSC growth than cisplatin with PD-1 antibody alone.<br /><br />The data suggest that Losartan inhibits AGTR1, impacting downstream pathways to suppress EMT, inhibit tumor angiogenesis and metastasis, and improve the tumor immune microenvironment. Consequently, Losartan could significantly bolster chemotherapy and chemoimmunotherapy outcomes in LUSC treatment.<br /><br />This research provides initial insights into the mechanisms through which ARBs like Losartan may function in LUSC therapy, suggesting its potential role as a valuable component in comprehensive treatment strategies. The study was presented at the IASLC 2024 World Conference on Lung Cancer, emphasizing its significance in the ongoing research into cancer treatment enhancements.

Asset Subtitle

Haiyu Zhou

Meta Tag

Speaker Haiyu Zhou

Topic Tumor Biology – Translational Biology

Keywords

Losartan

Lung Squamous Cell Carcinoma

chemotherapy

immunotherapy

tumor microenvironment

angiotensin receptor blocker

Epithelial-Mesenchymal Transition

zebrafish models

mouse models

AGTR1