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This is an important study from Dr. David Tran, et al. In this Phase I/IIb clinical trial, laser interstitial thermal therapy (LITT) was combined with the immune checkpoint inhibitor pembrolizumab for patients with recurrent high-grade gliomas (HGG), including glioblastoma. All patients were at least at their second recurrence, and several had reached their third (or greater) recurrence at time of entering the trial. LITT ablates tumor tissue with heat and temporarily opens the blood-brain barrier, but this study found that it also activates non-classical monocytes, priming the immune system so pembrolizumab can stimulate CD8+ T cell proliferation, clonal expansion, and memory responses. This approach, when compared with conventional non-LITT surgery followed by pembrolizumab, more than doubled median overall survival (OS) from 5.2 to 11.8 months and improved median progression-free survival (PFS) from 1.6 to 4.5 months in the per-protocol population (n = 39). Similarly, in the GBM (IDH-wildtype) sub-population (n = 34), median OS was doubled from 4.8 to 11.1 months, and median PFS increased from 1.7 to 3.9 months. Among all HGG patients in the per-protocol population treated with LITT + pembrolizumab, 42% were alive at 18 months, and over one-third survived more than 3 years.