Cancer Cell：华人团队揭示免疫治疗后癌症复发的新机制

Core Viewpoint - Cancer immunotherapy has revolutionized cancer treatment by activating the immune system to attack tumors, but many patients still face tumor recurrence, with underlying mechanisms not fully understood [1][4]. Group 1: Tumor-Initiating Stem Cells (tSC) - Tumor-initiating stem cells (tSC) are considered a key cell population responsible for tumor recurrence, yet their role in regulating the immune microenvironment remains largely unknown [1][5]. - Recent research indicates that tSC can survive during strong anti-tumor immune responses induced by immunotherapy, contributing to cancer recurrence post-treatment [5][10]. Group 2: Neutrophils in Tumor Microenvironment - Neutrophils, as one of the most abundant immune cells in the tumor microenvironment (TME), have a close relationship with the effectiveness of immunotherapy [1][4]. - Tumor-associated neutrophils (TAN) have been traditionally viewed as having immunosuppressive roles, but recent studies suggest they can enhance anti-tumor immune responses by presenting new antigens through MHCII molecules [1][6]. Group 3: Research Findings - A study published in Cancer Cell reveals that tSC regulate the plasticity of neutrophils through metabolic reprogramming, creating a protective niche that allows them to survive during cancer immunotherapy, leading to recurrence [2][10]. - The study identifies a specific signaling axis (SOX2-FADS1-PGE2) that could serve as a novel combination therapy strategy to prevent immunotherapy resistance and tumor recurrence [2][10]. Group 4: Implications of Findings - The research highlights the dynamic interactions between tSC and TAN, showing that effective immunotherapy can induce different responses in various TAN subpopulations [8][10]. - The findings suggest that targeting the PGE2 signaling pathway can restore the anti-tumor functions of neutrophils, enhancing the effectiveness of immunotherapy and significantly reducing tumor recurrence rates [7][12].