Abstract
Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir.
Highlights
Glioblastoma constitutes about half of all primary brain tumors and has a median survival time of 10 to 18 months with current standard treatment of maximal primary resection, irradiation, and temozolomide [1,2]
In the effort to find better treatments we reviewed past research on immunosuppressive lymphocytes in glioblastoma and looked for data that might indicate a clinically realizable path using currently available drugs to inhibit immunosuppressive lymphocytes
Since TDO is stimulated by cortisol and other adrenal corticosteroids [30] we suggest that one mechanism underlying stress-related Herpes labialis outbreaks is increased activity of TDO, which upregulates Treg activity
Summary
Glioblastoma constitutes about half of all primary brain tumors and has a median survival time of 10 to 18 months with current standard treatment of maximal primary resection, irradiation, and temozolomide [1,2]. Acyclovir may prolong survival of glioblastoma patients via its inhibition of thymidine kinase, which is expressed by CMV-infected cells Another antiviral agent, gancyclovir, is marginally more efficient than acyclovir against CMV and may be interesting to test as adjunct to current glioblastoma protocol, its inhibitory activity against IDO remains unknown. In accordance with our hypothesis of induction of IDO and recruitment of Tregs, a case study of a glioblastoma patient has described the development of a strong CMV-specific T cell response elicited by treatment with autologous tumor lysate-pulsed DCs [50]
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