美国哈佛医学院Peter K. Sorger研究组绘制出结直肠癌中状态转换和的免疫相互作用的3D图谱。2023年1月19日出版的《细胞》杂志发表了这项成果。

研究人员使用高度复用的组织成像、三维重建、空间统计和机器学习来识别出结直肠癌中已知的具有诊断和预后意义的形态学特征的基础细胞类型和状态。在高倍数标志物空间中对这些特征进行量化，研究人员揭示了从一种肿瘤形态到另一种肿瘤形态的反复转换，其中一些与致癌基因和表观遗传调节因子表达的长程梯度相吻合。在肿瘤侵袭边缘，肿瘤、正常细胞和免疫细胞相互竞争，T细胞抑制涉及多种细胞类型；三维成像显示，看似局部的二维特征，如三级淋巴结构，通常是相互连接的，并具有分级的分子特性。因此，虽然癌症遗传学强调了肿瘤状态离散变化的重要性，但整个样本成像显示了类似于发育中组织的大规模形态和分子梯度。

研究人员表示，晚期实体癌是肿瘤、免疫和基质细胞的复杂组合，其特点是瘤内变化大。

Title: Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer

Author: Jia-Ren Lin, Shu Wang, Shannon Coy, Yu-An Chen, Clarence Yapp, Madison Tyler, Maulik K. Nariya, Cody N. Heiser, Ken S. Lau, Sandro Santagata, Peter K. Sorger

Issue&Volume: 2023/01/19

Abstract: Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells characterized by high intratumoral variation. We use highly multiplexed tissue imaging, 3D reconstruction, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. Quantitation of these features in high-plex marker space reveals recurrent transitions from one tumor morphology to the next, some of which are coincident with long-range gradients in the expression of oncogenes and epigenetic regulators. At the tumor invasive margin, where tumor, normal, and immune cells compete, T cell suppression involves multiple cell types and 3D imaging shows that seemingly localized 2D features such as tertiary lymphoid structures are commonly interconnected and have graded molecular properties. Thus, while cancer genetics emphasizes the importance of discrete changes in tumor state, whole-specimen imaging reveals large-scale morphological and molecular gradients analogous to those in developing tissues.

DOI: 10.1016/j.cell.2022.12.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01571-9