Cancer Cell：张建军/吴佳/朱波团队发现肺癌的“癌前拦截”靶点——TIM-3

Core Viewpoint - Lung cancer remains the leading cause of cancer-related deaths globally, primarily due to late-stage diagnosis, emphasizing the critical need for early detection and intervention [1][11]. Group 1: Importance of Early Detection - Early diagnosis and intervention are crucial, with low-dose spiral CT screening significantly reducing lung cancer mortality rates [1]. - Understanding the molecular mechanisms of early lung cancer is vital for precise screening, diagnosis, prevention, and treatment [1]. Group 2: Challenges in Research - The study of early cancer development, particularly lung adenocarcinoma (LUAD), faces significant challenges due to the scarcity of precursor lesion specimens [1]. - Atypical adenomatous hyperplasia (AAH) is recognized as the only precursor lesion for lung adenocarcinoma, with potential progression to non-invasive adenocarcinoma in situ (AIS) and invasive adenocarcinoma (IAC) [1]. Group 3: Recent Research Findings - A recent study published in Cancer Cell identified TIM-3 as a potential target for lung cancer "precancer interception" through spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors [2]. - The research revealed a significant upregulation of TIM-3 in myeloid immune cells during the precancerous stage, suggesting its role in immune regulation within the tumor microenvironment [6][7]. Group 4: Immune Response Dynamics - The transition from precancerous lesions to invasive cancer is associated with changes in macrophage polarization and T cell functionality, indicating a shift from innate to adaptive immune responses [6]. - The study identified 818 spatial features related to immune checkpoint TIM-3, highlighting its central regulatory role in early tumor evolution [6]. Group 5: Therapeutic Implications - Blocking TIM-3 demonstrated significant potential for "precancer interception," effectively inhibiting the progression from precancerous lesions to invasive cancer in mouse models [8]. - The treatment not only reduced the proportion of pro-tumor M2 macrophages but also improved the immune surveillance of the precancerous microenvironment [8]. Group 6: Conclusion - The findings provide a crucial mechanistic basis for targeting immune suppression in precancerous stages and lay a solid foundation for early intervention strategies [11].