Glucocorticoids and immune checkpoint inhibitors in glioblastoma.

Abstract

Immunotherapy, activation of the immune system to target tumor cells, represents a paradigm shift in the treatment of cancer. Immune checkpoint therapies, which target immunomodulatory molecules expressed on T-lymphocytes, have demonstrated improved survival in a variety of malignancies. However, benefit in glioblastoma, the most common and devastating malignant brain tumor, remains to be seen. With several recent clinical trials failing to show efficacy of immunotherapy, concerns have been raised regarding the impact of glucocorticoid use in this patient population that may impair the ability for immune checkpoint inhibitors to affect a response. For this article we examined the mechanism by which immune checkpoint inhibitors activate, and glucocorticoids impair, T-lymphocyte function. In this context, we review the clinical data of immune checkpoint inhibitors in glioblastoma as well as the impact glucocorticoids have on immune checkpoint inhibitor efficacy. Finally, we highlight key questions that remain in the field, and the potential benefit of further research for central nervous system tumors. More information on the extent, character and duration of glucocorticoids on patients treated with PD-(L)1 will better inform both clinical management and novel therapeutic development of immunotherapy in patients with CNS malignancies.