Core Viewpoint - The article discusses a groundbreaking study published in Nature by a team led by Academician Zhang Zemin, focusing on the concept of "cross-tissue cellular modules" and their role in multicellular coordination within human tissues, particularly in the context of cancer progression [2][16]. Group 1: Research Background - The study integrates single-cell transcriptomic data from 706 healthy samples across 35 human tissues, creating the most comprehensive cross-tissue single-cell atlas to date, covering 2.29 million cells [8][16]. - The research identifies significant differences in cellular composition across various healthy tissues, revealing 12 distinct cross-tissue cellular modules (CMs) with unique cellular compositions and distributions [9][16]. Group 2: Cellular Modules and Their Functions - The identified cellular modules include CM04, CM05, CM06, and CM09, which are abundant in primary and secondary immune organs, indicating their roles in immune cell production and maturation [10][13]. - Other modules, such as CM02 and CM03, are primarily found in the urinary system and gastrointestinal tract, while CM08 is enriched in barrier tissues like skin and mucosal surfaces, suggesting their specific functional roles [10][11]. Group 3: Spatial Dynamics and Aging - The study employs spatial transcriptomics to illustrate how these cellular modules are spatially organized within tissues, highlighting their functional roles in maintaining tissue homeostasis [14][16]. - Notably, the immune cell modules CM05 and CM06 exhibit contrasting temporal dynamics with aging, where CM05 increases while CM06 decreases, indicating their potential as biomarkers for age-related changes [14][16]. Group 4: Implications for Cancer Research - The research extends to the tumor microenvironment (TME), analyzing single-cell transcriptomic data from 1,062 clinical samples across 29 cancer types, identifying 91 cell subpopulations [15][16]. - It reveals a dual remodeling of cellular modules during tumor progression, where healthy tissue-specific modules are lost, and cancer-associated modules emerge, providing insights into the fundamental organizational principles of multicellular ecosystems in health and disease [15][16].

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].

本文为IPO早知道原创 作者｜罗宾 微信公众号｜ipozaozhidao 已启动C2轮融资。 礼新医药创始人、董事长兼首席执行官秦莹博士表示："礼新医药自创立以来，一直坚持源头自主创 新，聚焦肿瘤微环境，专注于开发研发肿瘤特异性靶向ADC和免疫调节大分子创新药物，已建立了 一套完整覆盖从临床前直至临床III期的拥有自主知识产权并具有全球竞争力的差异化创新药管线。我 们将不负众望，加快推进LM-302和LM-108两个后期临床管线，争取早日实现产品上市。同时， 持续产出聚焦于肿瘤免疫及肿瘤微环境领域内尚未满足的治疗需求的早期源头创新管线，并继续积极 探索与各种伙伴以及各界展开多元化的紧密合作，通过BD合作进一步提升公司自我造血能力。" 中国生物制药有限公司董事会主席谢其润表示："中国生物制药已上市了安罗替尼等众多重要的肿瘤 产品，并且正持续不断地投入创新药研发与合作。我们一直关注肿瘤免疫治疗和ADC药物的研发进 展，礼新医药是一家聚焦于肿瘤免疫及肿瘤微环境领域的创新药公司，其差异化的创新管线布局、扎 实的GPCR多次跨膜蛋白抗体发现平台、双抗技术平台和ADC技术平台、都给我们留下了深刻的印 象。我们坚定看好礼新 ...