Tyler Miller, MD, PhD, a member of Case CCC's Immune Oncology Program, co-authored a new study in Cell examining why some patients with recurrent glioblastoma respond to CAR T-cell therapy while others do not.
Led by investigators at the University of Pennsylvania, the study used single-cell sequencing of tumor and cerebrospinal fluid samples collected before and after dual-target CAR T-cell treatment.
Researchers found that the pre-treatment immune environment strongly influenced therapeutic response. Tumors enriched with immunosuppressive myeloid cells were associated with poorer outcomes, while increased natural killer cell activity after therapy correlated with improved responses.
The findings suggest that targeting immune suppression within the glioblastoma microenvironment may improve the durability and effectiveness of CAR T-cell therapies.
Miller's laboratory previously identified this immunosuppressive myeloid cell program, and the new study validates its role as a potential predictor of treatment response. The work also demonstrates that cerebrospinal fluid immune profiling may offer a minimally invasive approach to monitoring the tumor immune environment without repeat brain biopsies.
The study advances efforts to develop more effective immunotherapies for glioblastoma and highlights the importance of multi-institutional collaboration in translational cancer research.