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.
Competing Interests: Declaration of interests A.C.A. is a member of the SAB for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, Zumutor Biologics, ImmuneOncia, and is a paid consultant for iTeos Therapeutics and Larkspur Biosciences, which have interests in cancer immunotherapy. A.C.A.’s interests were reviewed and managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict-of-interest policies.
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