Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor-Ligand Interactions That Instructs Intratumoral γδT-cell Activity.

ABSTRACT: The dynamic interplay between tumor cells and γδT cells within the tumor microenvironment significantly influences disease progression and immunotherapy outcome. In this study, we delved into the modulation of γδT-cell activation by tumor cell ligands CD112 and CD155, which interact with the activating receptor DNAM-1 on γδT cells. Spatial and single-cell RNA sequencing, as well as spatial metabolomic analysis, from neuroblastoma revealed that the expression levels and localization of CD112 and CD155 varied across and within tumors, correlating with differentiation status, metabolic pathways, and ultimately disease prognosis and patient survival. Both in vivo tumor xenograft experiments and in vitro coculture experiments demonstrated that a high CD112/CD155 expression ratio in tumors enhan

SUBMITTER: Wang X 

PROVIDER: S-EPMC11733534 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature