AbstractBackgroundRecurrence 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.MethodsWe 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.ResultsCryoablation 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.ConclusionsThis 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.