The landscape of glioma-infiltrated immune cells after immune checkpoint blockade treatment

Newswise — Despite the immune checkpoint blockade (ICB) having succeeded in multiple cancer therapies, high-grade gliomas such as glioblastoma multiforme (GBM) have a very low response rate to ICB, and GBM patients still do not benefit from ICB. To overcome this limitation, understanding the unique immunologic characteristics of brain tumors is needed. Here, we used single-cell RNA sequencing to analyze the macroscopic immune landscape of the tumor microenvironment (TME) under the treatment of ICB in a murine GBM model. CD8+ T cells showed both invigoration and exhaustion states, representing that CD8+ T cells show a mixed phenotype in the brain tumor. Furthermore, we found an increase in the number of anti-inflammatory macrophages in the TME after the ICB treatment, which is dependent on the increased CCL5 expression. Therefore, we hypothesized that the recruitment of anti-inflammatory macrophages mediated by CCL5 is associated with the exhaustion state of CD8 T cells and subsequent unresponsiveness of GBM against ICB. Finally, we compared our observations in the murine GBM model with publicly available data obtained from recurrent GBM patients. Our study provides critical information for the immune landscape of glioma after the ICB treatment and potentiates the development of novel immunotherapies to overcome the proposed limitations of ICB treatment.