Journal
CLINICAL CANCER RESEARCH
Volume 27, Issue 7, Pages 2038-2049Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-3262
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Funding
- NIH [R01 NS109742, F31 NS101771, F32 CA243314]
- Sontag Foundation
- Cleveland Clinic Research Program Committees grant
- Case Comprehensive Cancer Center
- Cleveland Clinic Brain Tumor Research and Therapeutic Development Research Center of Excellence
- Blast GBM
- Cleveland Clinic VeloSano Bike Race
- B~CURED
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This study investigated the impact of surgical resection and steroid treatment on antitumor immune response in GBM patients. They found that increased tumor volume before intervention correlates with reduced systemic immune function, and peripheral lymphocyte counts are prognostic even when considering steroid treatment.
Purpose: Glioblastoma (GBM) immunotherapy clinical trials arc generally initiated after standard-of-care treatment-including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment-has either begun or failed. However, the impact of these interventions on the antitumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the antitumor immune response has yet to be determined. Experimental Design: We developed a murine model integrating tumor resection and steroid treatment and used flow cytornetry to analyze systemic and local immune changes. These mouse model findings were validated in a cohort of 95 patients with primary GBM. Results: Using our murine resection model, we observed a systemic reduction in lymphocytes corresponding to increased tumor volume and decreased circulating lymphocytes that was masked by dexamethasone treatment The reduction in circulating 'I' cells was due to reduced CCR7 expression, resulting in T-cell sequestration in lymphoid organs and the bone marrow. We confirmed these findings in a cohort of patients with primary GBM and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Finally, we demonstrated that peripheral lymphocyte content varies with progression-free survival and overall survival, independent of tumor volume, steroid use, or molecular profiles. Conclusions: These data reveal that prior to intervention, increased tumor volume corresponds with reduced systemic immune function and that peripheral lymphocyte counts are prognostic when steroid treatment is taken into account.
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