Updates on Management of Adult Medulloblastoma

Majd, Nazanin; Penas‐Prado, Marta

doi:10.1007/s11864-019-0663-0

Cited by 46 publications

(41 citation statements)

References 109 publications

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“…In human trials so far, immune checkpoint inhibitors have failed as monotherapy in recurrent glioblastoma. 63,93 Lack of efficacy is believed due to minimal T cell infiltration into glioblastoma tumors, with similar findings reported in medulloblastomas. 63,90 One study showed that cytotoxic T cells infiltrate medulloblastomas with variable activation and do not correlate with increased survival.…”

Section: Checkpoint Inhibitors In Medulloblastomasupporting

confidence: 52%

“…63,93 Lack of efficacy is believed due to minimal T cell infiltration into glioblastoma tumors, with similar findings reported in medulloblastomas. 63,90 One study showed that cytotoxic T cells infiltrate medulloblastomas with variable activation and do not correlate with increased survival. 90 Medulloblastoma cells have decreased antigen presentation via downregulated MHC-1 expression of PD-L1.…”

Section: Checkpoint Inhibitors In Medulloblastomasupporting

confidence: 52%

“…The challenge of using dendritic cells is that it requires tumor collection from each patient, which results in extensive processing. 63 In another study, autologous monocyte-derived dendritic cells were loaded with tumor lysate, which served as a source of tumor antigens. 64 Patients with high-grade glioma and atypical teratoid-rhabdoid tumors responded more favorably to the vaccine treatment than the medulloblastoma patients.…”

Section: Vaccine Therapy In Medulloblastomamentioning

confidence: 99%

“…Thus, it is possible that PD-1/PD-L1 contributes to immune escape in medulloblastoma. 63 Nevertheless, the checkpoint inhibitors against PD-1, including nivolumab, pembrolizumab, and durvalumab, are each under investigation in clinical trials recruiting medulloblastoma patients and other CNS tumors (NCT03173950, NCT02359565, NCT02793466). Furthermore, nivolumab with and without ipilimumab, another checkpoint inhibitor that targets a different pathway known as CTLA-4, is also under investigation in a phase II trial of patients with high-grade CNS malignancies including medulloblastoma (NCT03130959).…”

Section: Checkpoint Inhibitors In Medulloblastomamentioning

confidence: 99%

“…96 Natural killer cells lyse tumor cells without immunization and secrete granules containing granzymes and perforin. 63,97 However, their efficacy is limited by immunosuppressive cytokines released in the medulloblastoma microenvironment such as transforming growth factor B (TGF-B). One study modified cord blood natural killer cells to express a dominant negative TGF-B receptor.…”

Section: Natural Killer Cells In Medulloblastomamentioning

confidence: 99%

See 4 more Smart Citations

<p>Immunotherapy for Medulloblastoma: Current Perspectives</p>

Kabir¹,

Kunos²,

Villanó³

et al. 2020

ITT

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Background: Immune-mediated therapies have transformed the treatment of metastatic melanoma and renal, bladder, and both small and non-small cell lung carcinomas. However, immunotherapy is yet to demonstrate dramatic results in brain tumors like medulloblastoma for a variety of reasons. Recent pre-clinical and early phase human trials provide encouraging results that may overcome the challenges of central nervous system (CNS) tumors, which include the intrinsic immunosuppressive properties of these cancers, a lack of antigen targets, antigenic variability, and the immune-restrictive site of the CNS. These studies highlight the growing potential of immunotherapy to treat patients with medulloblastoma, a disease that is a frequent cause of morbidity and mortality to children and young adults. Methods: We conducted an inclusive review of the PubMed-indexed literature and studies listed in clinicaltrials.gov using combinations of the keywords medulloblastoma, immunotherapy, CNS tumors, brain tumors, vaccines, oncolytic virus, natural killer, and CAR T to identify trials evaluating immunotherapy in preclinical experiments or in patients with medulloblastoma. Given a limited number of investigations using immunotherapy to treat patients with medulloblastoma, 24 studies were selected for final analysis and manuscript citation. Results: This review presents results from pre-clinical studies in medulloblastoma cell lines, animal models, and the limited trials involving human patients. Conclusion: From our review, we suggest that cancer vaccines, oncolytic viral therapy, natural killer cells, and CAR T therapy hold promise against the innate immunosuppressive properties of medulloblastoma in order to prolong survival. There is an unmet need for immunotherapy regimens that target overexpressed antigens in medulloblastoma tumors. We advocate for more combination treatment clinical trials using conventional surgical and radiochemotherapy approaches in the near-term clinical development.

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