Temporal multi-modal single-cell analyses reveal dynamic interactions of CAR-T cells with glioblastoma and targeting of antigen-negative neoplastic cells
Zhang, D. Y.; Wang, X.; Sun, Y.; Cui, Q.; Nelson, E.; Zhang, Z.; Huang, B.; Giles, J.; Thokala, R.; Connolly, D. R.; Jacob, F.; Wherry, J.; Lucas, T.; Chen, I. H.; Shi, Y.; Binder, Z. A.; Brem, S.; Nasrallah, M.; Salinas, R.; O'Rourke, D. M.; Ming, G.-L.; Song, H.
Show abstract
CAR-T therapy is a promising new immunotherapy for cancers, but its efficacy for solid tumors requires improvement. A detailed understanding of the interplay between solid tumors and CAR-T cells is critical. Here we report temporal, multi-modal, single-cell profiling of patient-derived glioblastoma organoids with CAR-T treatment. We found that all tumor cell types responded to CAR-T cell activation and contributed to an initially anti-tumor, but subsequently pro-tumor and immune-inhibitory microenvironment, accompanied by CAR-T cell exhaustion. Unexpectedly, CAR-T treatment attenuated glioma stem-like states of both antigen-positive and antigen-negative neoplastic cells and reduced their proliferation via diffusible factors, including IFN{gamma}. Analysis of samples from additional patients, including those in clinical trials, supported these findings. Our study reveals the dynamic interplay among different tumor cells and T cells in adaptive responses to immunotherapy and identifies previously unappreciated benefits of CAR-T therapy directly on antigen-negative neoplastic cells that may be leveraged to enhance therapeutic efficacy.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy 98%
- Glioma-neuronal circuit remodeling induces regional immunosuppression 97%
- Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations 97%
Similar papers in this journal
Similar papers in this journal
- Cell lineage as a predictor of immune response in neuroblastoma 96%
- Cancer-associated fibroblast compositions change with breast cancer progression linking S100A4 and PDPN ratios with clinical outcome 96%
- A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma 96%
Similar papers in this journal
- Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma 96%
- Precision combination therapies based on recurrent oncogenic co-alterations 96%
- Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.