Introduction: Regulatory T cells (Tregs) have an immunosuppressive function that can promote tumor growth in numerous malignancies. Prior studies have shown that Tregs as a fraction of the CD4+ T cell population are expanded within the tumor microenvironment and peripheral blood of GBM patients. Differing studies have shown mixed associations between the presence of intratumoral Tregs and GBM patient survival. Although circulating Tregs have been shown to impact survival in preclinical models of GBM, no clear association has been demonstrated clinically in patients. Here, we investigate the clinical impact of peripheral Treg expansion in newly diagnosed GBM patients receiving standard treatment.
Methods: Peripheral blood leukocytes were isolated from 61 newly diagnosed GBM patients prior to surgery. Tregs (CD4+CD25+FoxP3+) were quantified by flow cytometry, and patients were divided into Treghi and Treglo subsets relative to the median. All patients underwent maximal safe resection followed by standard chemoradiation. Radiographic progression and overall survival were recorded.
Results: Peripheral Treg populations ranged from 0.3-14.3%, with a mean of 4.5%. Median progression free survival (PFS) for all patients was ¬¬9.5 months and median overall survival (OS) was 14.8 months. PFS for the Treghi and Treglo groups was 9.0 and 11.2 months, respectively (HR = 0.91; p=0.77). OS for the Treghi and Treglo groups was 14.8 and 16.1 months, respectively (HR = 0.95; p=0.89). Patients in the bottom quartile were compared to the top quartile without statistically significant differences in PFS (HR = 0.64; p=0.33) or OS (HR = 0.58; p=0.24).
Conclusions: In patients receiving standard of care treatment for newly diagnosed GBM, Treg expansion in peripheral blood does not significantly impact survival. As the use of immune checkpoint targeting therapies, including the Treg targets CTLA-4 and CD25, are increasingly used in the management of cancer, these findings should be strongly considered when designing studies for GBM.
Patient Care: A role for Treg-induced immunosuppression within the GBM tumor microenvironment has been well established and is popularly being considered for immunotherapeutic strategies. We demonstrate, however, that the peripheral abundance of the Treg subset does not impact progression or survival. These findings should be strongly considered when designing studies for GBM.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Describe the importance of Treg prominence in the setting of GBM,
2) Discuss, in small groups, the clinical outcomes associated with high and low Treg fractions in GBM patients,
3) Identify an effective treatment that targets Treg-derived immunosuppression.