肿瘤的发生和进展可以通过经历上皮间质转化（EMT）的肿瘤细胞、侵袭因子和免疫细胞之间复杂的相互作用来确定。在本研究中，我们采用单细胞RNA测序（scRNA-seq）和空间分辨转录组学（ST）来评估原发性结直肠癌（CRC）组织中EMT侵袭性恶性肿瘤与免疫细胞之间的伪时间轨迹和空间相互作用关系。不同阶段（I/II 期和有肿瘤沉积的 III 期）。我们的研究通过构建位于 ST 边缘的伪时间终点 EMT 入侵肿瘤程序（EMTP），利用与 EMT 入侵基因集成的进化轨迹分析来表征不同侵袭性肿瘤程序之间的时空关系。引人注目的是，肿瘤的侵袭和扩张过程经历了调节性和免疫抑制细胞的显着空间重编程，例如骨髓源性抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）、调节性 T 细胞（Treg）和耗尽的 T 细胞。特克斯）。这些 EMTP 邻近细胞与 EMT 相关的侵袭基因相关，尤其是对 CRC 预后很重要的 C-X-C 基序配体 1 (CXCL1) 和 CXCL8 基因。有趣的是，I 期的 EMTP 主要产生炎症边缘侵袭生态位，而 III 期组织中的 EMTP 可能产生缺氧的侵袭前生态位。我们的数据证明了调节细胞和免疫抑制细胞在结直肠癌肿瘤形成和进展中的关键作用。这项研究提供了一个框架来描绘 CRC 样本中的时空侵入生态位。© 2023。作者。

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.© 2023. The Author(s).