卵巢癌（OvCa）是最致命的妇科恶性肿瘤。免疫检查点抑制剂彻底改变了多种恶性肿瘤的治疗，但对 OvCa 患者的疗效有限。这种有效性的缺乏部分是由于卵巢肿瘤微环境（TME）异常，显示出促纤维增生、高度纤维化的细胞外基质。高细胞外基质沉积导致压力积聚，导致肿瘤血管塌陷、血管灌注减少、药物输送不良以及细胞毒性 T 细胞向这些肿瘤的运输受损。使用两个同基因 OvCa 模型，我们测试了氯沙坦是一种广泛使用的抗高血压药物，致力于对 TME 进行重编程并使癌细胞化学敏感。氯沙坦治疗 (i) 对 TME 进行重编程，导致血管灌注增加，从而增强药物输送和免疫效应细胞瘤内浸润和功能； (ii) 通过抑制 IGF-1 信号传导重新连接 OvCa 细胞，从而增强化疗敏感性。由于肿瘤和基质效应的综合作用，氯沙坦治疗增强了 OvCa 模型中化学免疫疗法的疗效。氯沙坦的安全性和低成本（ < $1-2/天）保证了我们的研究结果能够快速转化为 OvCa 患者。 © 2024。作者获得施普林格自然有限公司的独家许可。

Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors.Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells.Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models.The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.