![]() Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z et al (2008) CTLA-4 control over Foxp3 + regulatory T cell function. Krummel MF, Allison JP (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. Jacobs JF, Idema AJ, Bol KF, Nierkens S, Grauer OM, Wesseling P et al (2009) Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. J Clin Oncol 36(14):1428–1439įreeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. N Engl J Med 379(22):2108–2121Īrmand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL et al (2018) Nivolumab for relapsed/refractory classic hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 Trial. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D et al (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. 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. Finally, we highlight key questions that remain in the field, and the potential benefit of further research for central nervous system tumors. 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. Methodsįor this article we examined the mechanism by which immune checkpoint inhibitors activate, and glucocorticoids impair, T-lymphocyte function. 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. However, benefit in glioblastoma, the most common and devastating malignant brain tumor, remains to be seen. Immune checkpoint therapies, which target immunomodulatory molecules expressed on T-lymphocytes, have demonstrated improved survival in a variety of malignancies. Immunotherapy, activation of the immune system to target tumor cells, represents a paradigm shift in the treatment of cancer.
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