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研究摘要
Among patients with bladder cancer, non-muscle invasive bladder cancer (NMIBC) which has a much more favorable prognosis than muscle-invasive bladder cancer. However, preventing the recurrence of NMIBC post-transurethral resection (TUR) remains challenging and bladder cancer therapy remains suboptimal as the morbidity and mortality remains high amongst those with non-muscle invasive and muscle-invasive disease. Recently, bladder intracavitary hyperthermic perfusion chemotherapy or concurrent radiotherapy can significantly improve the therapeutic effect, which was consequently sparked a renewed interest in using this therapeutic modality to treat bladder cancer. Nonetheless, monotherapy can often cause resistance to therapeutic modalities that can be immunologically classified as primary, adaptive, or acquired, and involve an innate refractory response or a development of an avoidance mechanism by the tumor or tumor microenvironment. Importantly, when immunotherapy is combined with loco-regional hyperthermia, it has demonstrated enhanced tumor responses. Since heating tumors activates the immune system at least partly through increased and released HSPs and some chemotherapy drugs also depend for their efficacy on HSPs, these two therapies may work additively, for example by enhancing tumor antigen presentation by antigen-presenting cells (APCs) through increased total HSP release by tumor cells. Unfortunately, according to statistical analysis of clinical data, a proportion of patients exhibit resistance to hyperthermia as adjuvant treatment for malignant tumor. To date, there is lack effective temperature control or regulation, and cannot provide uniform distribution of heat to the bladder. As such, there’s now a pressing need of developing novel strategies to overcome the immunosuppressive mechanisms in bladder cancer as well as clinically validated immune markers that can more accurately predict the response to therapy and to determine the duration and intensity of the hyperthermic exposures. Although there is still much room for improvement, emerging evidence demonstrates the potential of local hyperthermia therapy as a powerful tool to support other emerging approaches to cancer immunotherapy. In order to develop effective prediction models and optimal therapeutic protocols of hyperthermia in bladder cancer therapy, this project proposed by a group of active basic and clinical researchers in the fields of bladder cancer represents an integrated effort aiming at overcoming the resistance of malignant tumor cells to hyperthermia therapy and underlying mechanisms of action in the therapeutic response. We expect that the projects proposed will unveil the potential of novel immunological markers and develop the optimal treatment protocols in the prognosis and the treatment of carcinoma in situ of the urinary bladder, and also may pave the road for the subsequent clinical developments and clinical trials.
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