Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Fudan Institute of Urology, Fudan University, Shanghai, China.
Clin Transl Med. 2023 May;13(5):e1255. doi: 10.1002/ctm2.1255.
Recurrence and metastasis of bladder cancer are major factors affecting patient prognosis. Endoscopic cryoablation achieved a better clinical outcome among clinical patients and could be synergistic with ICIs. Thus, this study aimed to evaluate the immunological mechanism of cryoablation for bladder cancer to reveal the therapeutic mechanism.
We systematically reviewed the clinical prognosis of patients underwent cryoablation at Huashan Hospital in these first-in-human studies (ChiCTR-INR-17013060). Murine models were constructed to explore cryoablation-induced tumour-specific immunity, which was further confirmed by primary bladder tumour organoids and autologous lymphocytes cocultured system.
Cryoablation improved progression-free survival and recurrence-free survival respectively. Assessment of murine models after cryoablation confirmed microenvironment remodelling and tumour-specific T cells expansion. Enhanced antitumour effects were found after coculture of organoids with autologous lymphocytes collected from post-cryoablation. We also demonstrated cryoablation-induced tumour elimination required IFNGR expression on tumour cells. In addition, a long-lasting antitumour memory response is achieved by cryoablation and could be enhanced after combination with ICIs.
This study revealed endoscopic cryoablation is an efficient and safe therapy for bladder tumour treatment. The tumour-specific immune responses induced by cryoablation could reduce tumour recurrence and metastasis.
膀胱癌的复发和转移是影响患者预后的主要因素。内镜下冷冻消融在临床患者中取得了更好的临床效果，并且可以与免疫检查点抑制剂（ICIs）协同作用。因此，本研究旨在评估冷冻消融治疗膀胱癌的免疫机制，以揭示其治疗机制。
我们在华山医院的这些首次人体研究（ChiCTR-INR-17013060）中系统地回顾了接受冷冻消融治疗的患者的临床预后。构建了小鼠模型以探索冷冻消融诱导的肿瘤特异性免疫，进一步通过原发性膀胱癌类器官和自体淋巴细胞共培养系统进行了验证。
冷冻消融分别提高了无进展生存期和无复发生存期。对冷冻消融后小鼠模型的评估证实了微环境重塑和肿瘤特异性 T 细胞的扩增。在与冷冻消融后收集的自体淋巴细胞共培养后，观察到增强的抗肿瘤效果。我们还证明了冷冻消融诱导的肿瘤消除需要肿瘤细胞上的 IFNGR 表达。此外，冷冻消融可实现持久的抗肿瘤记忆反应，并且与 ICIs 联合使用可以增强这种反应。
本研究揭示了内镜下冷冻消融是治疗膀胱癌的一种有效且安全的治疗方法。冷冻消融诱导的肿瘤特异性免疫反应可降低肿瘤复发和转移的风险。
