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Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct
Johan Söderlund1, Sophie Erhardt, Richard E Kast
1Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Journal of Neuroinflammation
|August 10, 2010
Summary
Regulatory T cells (Tregs) are elevated in glioblastoma. The antiviral drug acyclovir inhibits IDO, an enzyme that promotes Tregs, suggesting it may reduce Treg function in glioblastoma patients.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Regulatory T cells (Tregs) possess immunosuppressive functions and are elevated in glioblastoma (GBM) patients' blood and tumors.
- Indoleamine 2,3-dioxygenase (IDO) activity is implicated in enhancing Treg formation through incompletely understood mechanisms.
- Experimental data in rodents show that IDO inhibition reduces Treg function and number.
Purpose of the Study:
- To investigate the potential of acyclovir, an IDO inhibitor, to modulate Treg populations in the context of glioblastoma.
- To establish the feasibility of assessing acyclovir's impact on Treg counts in pre-operative glioblastoma patients.
Main Methods:
- Confirmation of elevated Treg counts in glioblastoma tumor tissue.
- A small clinical trial administering acyclovir to pre-operative glioblastoma patients.
- Quantification of Treg counts in tumor tissue before and after acyclovir treatment.
Main Results:
- The study hypothesizes that elevated Tregs in glioblastoma can be targeted.
- Acyclovir's IDO inhibitory action is proposed as a mechanism to decrease Treg function and number.
- The potential for acyclovir to reduce Treg counts in glioblastoma patients requires clinical validation.
Conclusions:
- Acyclovir may represent a therapeutic strategy to reduce Treg-mediated immunosuppression in glioblastoma.
- Further clinical trials are warranted to evaluate acyclovir's efficacy and impact on survival in glioblastoma patients, given its safety profile.
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