Spatial determinants of CD8⁺ T cell differentiation in cancer

Uncovering the mechanisms that control CD8⁺ T cell function is a major focus of cancer research. Advances in flow cytometry and single-cell transcriptomics have provided unprecedented in-depth resolution of CD8⁺ T cell states in cancer. However, these technologies fail to capture important spatial information, including cell-cell interactions and tissue localization. The discovery that intra-tumoral immune niches, tertiary lymphoid structures, and the tumor-draining lymph node are key sites of inter-cellular communication has evoked interest in understanding the spatial determinants that regulate CD8⁺ T cell functions at these sites. We focus on the cellular, as well as the soluble and surface-bound signals that regulate CD8⁺ T cell phenotypes and functions in a topologically-regulated manner, highlighting where new spatial transcriptomics and imaging technologies can uncover mechanistic insights.