Cancer Discovery：周圣涛/蓝春燕/黄欣/赵林桔等揭示晚期宫颈癌免疫再挑战响应的时空免疫决定因素

Core Viewpoint - The article discusses the potential of immune rechallenge therapy in advanced cervical cancer, highlighting recent research that demonstrates its efficacy and the underlying immune mechanisms involved [3][4][11]. Group 1: Research Findings - A study published in Cancer Discovery evaluated the efficacy of PD-1 antibody Zimberelimab combined with Lenvatinib in patients with advanced cervical cancer who progressed after initial immunotherapy, showing a 33.3% objective response rate and over 90% disease control rate [4][5]. - The median progression-free survival was reported at 7.1 months, with the median overall survival not yet reached, indicating a promising outcome for a subset of patients [5]. Group 2: Mechanisms of Action - The research utilized single-cell RNA sequencing and other multi-omics techniques to analyze immune responses, revealing that the effectiveness of immune rechallenge is linked to the functional state and evolutionary trajectory of CD8 T cells rather than their quantity [7]. - Responding patients exhibited a trend towards differentiation into effector memory T cells and cytotoxic T cells, enhancing their anti-tumor capabilities, while non-responders showed signs of T cell exhaustion [7]. Group 3: Predictive Biomarkers - A novel cell population termed "dyad cells," which co-express T cell and myeloid markers, was identified as a potential biomarker for predicting the efficacy of immune rechallenge, with baseline levels correlating with treatment outcomes [9]. - The abundance of dyad cells in baseline blood samples was shown to effectively predict the success of immune rechallenge, with an AUC of 0.886, suggesting their role in a highly synergistic immune activation state [9]. Group 4: Implications for Future Treatment - The study provides a new therapeutic strategy for patients who have previously failed immunotherapy, emphasizing the importance of functional CD8 T cells, macrophages, and dyad immune structures in achieving successful outcomes [11]. - This research lays a scientific foundation for patient stratification, efficacy prediction, and optimization of combination strategies in future treatments for advanced cervical cancer [11].