Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.
免疫检查点抑制剂疗法已被证实对某些癌症的治疗具有革命性意义。然而，卵巢癌对当前主流的免疫检查点抑制剂（如抗PD1或抗PD-L1抗体）仍缺乏反应。本文通过同源原位小鼠模型（ID8-fLuc），探讨了新兴检查点分子T细胞免疫球蛋白和黏蛋白结构域3在卵巢癌治疗中的潜力。除治疗效果外，我们重点研究了肿瘤组织和腹腔液中的免疫变化。结果显示，无论是单药治疗还是与抗PD1抗体或标准化疗（卡铂/紫杉醇）联合使用，抗TIM3治疗均未能改善荷卵巢癌小鼠的生存期。与对照组相比，治疗组小鼠的肿瘤免疫浸润情况未见改变。在联合治疗方案中调整给药顺序虽改变了生存结果，但未能产生优于单纯化疗的生存获益。这些发现表明，需要开展进一步的临床前研究，以寻找对卵巢癌有益的治疗方案和联合疗法。
TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice
肿瘤(癌症)患者之家