Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
Simonds EF, Lu ED, Badillo O, et al. JITC (2021)
The team Simonds, Lu, & Badillo et al. sought to determine why glioblastoma, the most common malignant brain tumor, is also the most resistant to immunotherapy. Using mass cytometry, the team compared the immune cell populations in two immune checkpoint refractory tumor types, glioblastoma and sarcoma, to renal cell carcinoma (immune checkpoint inhibitor-responsive). Deep immune profiling identified new potential targets among DC and tumor associated macrophage populations.
Single cell profiling of 19 glioblastoma, 11 renal cell carcinoma, and 4 sarcoma tumors was performed using mass cytometry. The team discovered that immunotherapy refractory glioblastoma tumors had very few T cells and a high frequency of myeloid cells while immunotherapy sensitive renal cell carcinoma tumors showed the opposite pattern. Evidence from the team’s mass cytometry profiling points to regulatory T cells as a key player in this system. They observed that FLT3L monotherapy caused expansion of DC and Tregs in tumor draining lymph nodes. The team showed that treatment of intracerebral immune checkpoint-refractory tumors in mice, with a recombinant FLT3-ligand, expanded DCs, boosted tumor-specific CD4 T cell priming, and prolonged survival.
Their data suggests that accurate tumor models and deep immune profiling can be leveraged to further explain the immunosuppressive mechanisms that are unique to brain tumors. These new insights provide resolution on how to better approach, treat and cure, therapy-refractory cancers.
Reference citation: Simonds EF, Lu ED, Badillo O, et al. Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma. Journal for ImmunoTherapy of Cancer 2021;9:e002181. doi: 10.1136/jitc-2020-002181