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.