Mapping intratumoral myeloid-T cell interactomes at single-cell resolution reveals targets for overcoming checkpoint inhibitor resistance.

ABSTRACT: Effective cancer immunotherapies restore anti-tumor immunity by rewiring cell-cell communication. Treatment-induced changes in communication can be inferred from single-cell RNA-sequencing (scRNA-seq) data, but current methods do not effectively manage heterogeneity within cell types. Here we developed a computational approach to efficiently analyze scRNA-seq-derived, single-cell-resolved cell-cell interactomes, which we applied to determine how agonistic CD40 (CD40ag) alters immune cell crosstalk alone, across tumor models, and in combination with immune checkpoint blockade (ICB). Our analyses suggested that CD40ag improves responses to ICB by targeting both immuno-stimulatory and immunosuppressive macrophage subsets communicating with T cells, and we experimentally validated a spatial ba

SUBMITTER: Bridges K 

PROVIDER: S-EPMC11565996 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature