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| EDITORIAL |
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| Year : 2019 | Volume
: 2
| Issue : 1 | Page : 1-2 |
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Glioma special issue introduction
Christopher Jackson, Michael Lim
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| Date of Web Publication | 1-Apr-2019 |
Correspondence Address:
Michael Lim
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD
USA
 Source of Support: None, Conflict of Interest: None  | 11 |
DOI: 10.4103/glioma.glioma_2_19
How to cite this article:
Jackson C, Lim M. Glioma special issue introduction. Glioma 2019;2:1-2 |
In the past decade, cancer immunotherapy has emerged from experimental protocols in select pathologies to a mainstay of frontline cancer therapy that has drastically improved outcomes for thousands of patients. Since the approval of the first anticancer vaccine (sipuleucel-T) in 2010, strategies for stimulating the immune system to fight cancer have evolved from monotherapy vaccination approaches adapted from infectious diseases to immune checkpoint inhibition, adoptive cell therapy, viral therapy, and many others. These clinical advances reflect pivotal discoveries in how the immune system interacts with the tumor microenvironment, leading to the identification of targetable pathways and rationally designed algorithms that account for pathology, patient, and iatrogenic factors. Despite the challenges of treating gliomas with immunotherapy, intensive efforts aimed at elucidating the underpinnings of glioma immunology and next-generation immunotherapeutic strategies have placed successful translation of the first glioma immunotherapies seemingly within reach.
Gliomas are immunologically complex tumors due to multiple, nonredundant immunosuppressive mechanisms.[1] These include not only glioma intrinsic factors, such as expression of checkpoint molecules and secretion of immunosuppressive cytokines,[2] but also local recruitment of immunosuppressive myeloid cells[3] as well as systemic tolerance mediated by inhibition of effector function and T-cell sequestration.[4],[5] Furthermore, standard-of-care radiation and chemotherapy thwarts antitumor immune responses and prevents generation of immunologic memory in preclinical models.[6],[7] Given these obstacles, it is perhaps not surprising that initial Phase III trials of immunotherapy for glioblastoma failed to meet their primary endpoints.[8],[9]
More detailed analysis of data from these and other studies, however, suggests that the immune system is capable of recognizing and eliminating gliomas. A low response rate (8%) prevented a Phase III study of nivolumab (CheckMate 143, NCT02017717) from meeting its primary endpoint of overall survival; however, survival was significantly longer for nivolumab responders than patients responding to bevacizumab (11.1 vs. 5.3 months).[10] In addition, there is indirect evidence for baseline antitumor immune activity as lymphopenia correlates with worse prognosis in glioblastoma patients.[11] Taken together, these findings, along with a large body of preclinical data, warrant redoubled efforts in developing novel, potent, and glioma-specific immunotherapeutic approaches.
This special issue of glioma focuses on selected topics at the leading edge of glioma immunology research. We have invited visionary leaders in the field to share their expertise on the current state of glioma immunotherapy and discuss critical next steps. The article on mechanisms of immune suppression by Piotrowski et al. discusses the factors that make treating glioma patients with immunotherapy singularly complex and sets the stage for the chapters that follow. Immune checkpoint inhibitors have been at the epicenter of immunotherapy for solid tumors and showed promise in glioma models, but clinical trial results have been mixed. Nduom et al. explicate the nuances of these data and place them in context. Ahluwalia et al. review the promising field of oncolytic viruses, which have shown potential in initiating strong antitumor immune responses against glioma antigens. Adoptive cell therapy has demonstrated impressive results in hematologic and some solid malignancies. Sengupta reviews how natural killer T cells may circumvent the challenge of identifying targetable glioma-specific antigens.
We envision that compiling ideas in this format will not only provide readers with a solid understanding of the state of the art in glioma immunotherapy but also afford a platform for synthesizing the ideas and insights necessary to develop groundbreaking therapeutic approaches for this devastating disease.
| References | |  |
| 1. | Lynes J, Sanchez V, Dominah G, Nwankwo A, Nduom E. Current options and future directions in immune therapy for glioblastoma. Front Oncol 2018;8:578.  |
| 2. | Woroniecka K, Chongsathidkiet P, Rhodin K, Kemeny H, Dechant C, Farber SH, et al. T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma. Clin Cancer Res 2018;24:4175-86. |
| 3. | Garzon-Muvdi T, Theodros D, Luksik AS, Maxwell R, Kim E, Jackson CM, et al. Dendritic cell activation enhances anti-PD-1 mediated immunotherapy against glioblastoma. Oncotarget 2018;9:20681-97. |
| 4. | Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med 2018;24:1459-68. |
| 5. | Jackson CM, Kochel CM, Nirschl CJ, Durham NM, Ruzevick J, Alme A, et al. Systemic tolerance mediated by melanoma brain tumors is reversible by radiotherapy and vaccination. Clin Cancer Res 2016;22:1161-72. |
| 6. | Piotrowski AF, Nirschl TR, Velarde E, Blosser L, Ganguly S, Burns KH, et al. Systemic depletion of lymphocytes following focal radiation to the brain in a murine model. Oncoimmunology 2018;7:e1445951. |
| 7. | Mathios D, Kim JE, Mangraviti A, Phallen J, Park CK, Jackson CM, et al. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM. Sci Transl Med 2016;8:370ra180. |
| 8. | Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial. Lancet Oncol 2017;18:1373-85. |
| 9. | Filley AC, Henriquez M, Dey M. Recurrent glioma clinical trial, checkMate-143: The game is not over yet. Oncotarget 2017;8:91779-94. |
| 10. | Jackson CM, Lim M. Immunotherapy for glioblastoma: Playing chess, not checkers. Clin Cancer Res 2018;24:4059-61. |
| 11. | Grossman SA, Ye X, Lesser G, Sloan A, Carraway H, Desideri S, et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 2011;17:5473-80. |
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