Seminario Dr. Maria Alieva, Instituto de Investigaciones Biomédicas "Alberto Sols" Salón de Grados E.T.S.I.I

Single-cell analysis is a valuable tool for analyzing the complexity of biological systems, but it only captures a snapshot of cellular processes at a particular timepoint. To understand cellular behavior and function, it is crucial to develop technologies that can investigate individual cell dynamics within a population. This is especially important for T cell immunotherapy, which has shown limited efficacy against solid tumors. 

To better understand T cell function, we have developed BEHAV3D, a dynamic immuno-organoid 3D imaging-transcriptomics platform, to investigate the solid tumor-targeting strategy of engineered immune cells. This platform revealed high heterogeneity in targeting efficacy and functional behavior of T cells, including a 'super engager' cluster with potent killing abilities. Transcriptomic analysis identified specific gene signatures linked to these behaviors, including 27 genes with no previously known T cell function. We also showed that type 1 interferon can prime resistant breast cancer for TEG-mediated killing. BEHAV3D provides a comprehensive platform for characterizing the heterogeneity of T cell immunotherapies against breast cancer, that is now also applied to study cooperation mechanisms between different subsets of T cells driving cancer targeting, or to investigate heterogenous responses to treatment between but also withing patients.