Altered intratumoral immune composition after Nivolumab treatment in patients with recurrent glioblastoma

Abstract Glioblastoma is an aggressive brain tumor with poor prognosis, and consequently immunotherapy is being explored as a potential treatment option. However, it is unclear whether systemic immunotherapy can reach and modify the tumor microenvironment in the brain. We evaluated immune characteristics in tumor and blood samples from recurrent glioblastoma patients, who received Nivolumab and Bevacizumab. One group received Nivolumab one week prior to surgery, and immune characteristics of the tumor were compared to control patients receiving salvage resection without prior Nivolumab treatment. Nivolumab-bound T-cells could be detected in tumor tissue, along with increasing numbers of both activated and differentiated CD4+ and CD8+ T-cells. An associated upregulation of co-inhibitory receptors on T-cells was observed following Nivolumab treatment. Additionally, tumor-reactivity was detected in tumor infiltrating lymphocytes (TILs) from Nivolumab-treated patients, and neoantigen-reactive T-cells could be identified in both TILs and blood, indicating a systemic response towards GBM in a subset of patients.