STEM-10. TEMPORAL MULTI-MODAL SINGLE-CELL ANALYSES REVEAL DYNAMIC INTERACTIONS BETWEEN GLIOBLASTOMA AND CAR-T CELLS AND IMMUNOLOGIC MODULATORS OF CANCER STEM CELL STATE

Abstract CAR-T cell therapy is a promising new immunotherapy for number of difficult-to-treat cancers, however, it has yet to yield broad success in glioblastoma (GBM). In particular, tumor heterogeneity presents major therapeutic challenge, and detailed understanding the complex interplay between different neoplastic, non-neoplastic, cells critical developing better treatments. Using patient-derived GBM organoid model therapy, we performed single-cell multi-omics examine longitudinal dynamics adaptive response, changes states, evolution cell-to-cell interaction networks. We find that all types - neoplastic non-neoplastic respond activity, they generate an initially anti-tumor, but subsequently pro-tumor immune-inhibitory microenvironment, which accompanied by eventual dysfunction exhaustion. Unexpectedly, activity also leads attenuation glioma stem-like states both antigen-positive antigen-negative reduces their proliferation via diffusible factors, IFNɣ required not sufficient. These findings are supported analyses patient samples from clinical trials, consistent across de novo recurrent tumors with somatic mutational landscapes. Our study unravels how interacts identify previously unappreciated possibilities affect ways may be further augmented enhanced efficacy.