Nature：华人团队开发新型PROTAC，治疗多种癌症类型，一作将回国加入南京大学

Core Viewpoint - Immune checkpoint blockade (ICB) therapies, represented by anti-PD-1 and anti-PD-L1 monoclonal antibodies, have significantly transformed cancer treatment, yet many patients show poor response or develop resistance to these therapies [2][6]. Group 1: Research Findings - A study published in Nature by a team from the University of Michigan reveals that the balance between STAT5 and STAT3 shapes dendritic cell (DC) function and tumor immunity, leading to the development of a STAT3-targeting PROTAC that enhances tumor sensitivity to ICB therapy [3][10]. - The research indicates that the limited number and impaired function of dendritic cells in the tumor microenvironment (TME) hinder the effectiveness of ICB therapies, emphasizing the need to understand the mechanisms behind dendritic cell phenotype formation [6][8]. Group 2: Mechanisms of Action - STAT3 is often activated in the TME, mediating immune suppression and promoting tumor growth factors, while STAT5 is activated by cytokine signals and plays a positive role in anti-tumor immune responses [7][9]. - The study found that ICB therapy reprograms the interaction between STAT3 and STAT5 pathways in dendritic cells, activating T cell immunity and enhancing the efficacy of ICB [9][10]. Group 3: Therapeutic Implications - The development of STAT3 degradation agents, such as SD-36 and SD-2301, shows promise in reprogramming dendritic cells towards an immunogenic state, effectively treating advanced tumors and those resistant to ICB therapy without toxicity [9][10]. - This research opens new avenues for cancer immunotherapy by targeting the dynamic balance between STAT3 and STAT5 in dendritic cells [10].