The anti-tumor function of CD8+T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+T and CD4+T cell-enriched neighborhoods enriched the majority of CD8+T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+T cells in this spatial architecture were significantly closer to themselves and the CD4+T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.
CD8+T细胞的抗肿瘤功能取决于其与肿瘤细胞的邻近程度。现有研究多聚焦于肿瘤微环境中CD8+T细胞的浸润水平，而对其空间定位及细胞间通讯等更深层次的空间信息尚未明确。本研究采用索引共检测技术，通过七种蛋白标志物对胰腺导管腺癌组织区域进行表征，以揭示调控人胰腺导管腺癌中CD8+T细胞的空间结构特征。运用细胞邻域算法共识别出六个保守且特征鲜明的细胞邻域。其中，一个富含CD8+T和CD4+T细胞的独特空间结构虽聚集了大部分CD8+T细胞，却预示着不良预后。邻近性分析显示，该空间结构中的CD8+T细胞与自身及CD4+T细胞的邻近程度显著高于其与肿瘤细胞的邻近程度。本研究系统鉴定出一种限制CD8+T细胞在肿瘤微环境中接近肿瘤细胞的独特空间结构，揭示了胰腺导管腺癌通过拓扑调控实现免疫逃逸的新机制，为深入理解PDAC生物学特性提供了新视角。
肿瘤(癌症)患者之家