IMMU-75. Cytokine Kinetics During Radiation Therapy in Glioblastoma Predict Survival

BACKGROUND Radiation therapy affects a wide range of circulating lymphocyte subpopulations that are integral to mounting a successful lymphocyte-mediated immune response. Lymphopenia is associated with inferior tumor control and could be addressed to improve outcomes in glioblastoma. RT is a significant and potentially actionable iatrogenic suppressor of immune response that may limit the success of therapy. We hypothesized that a comprehensive evaluation of serial cytokine measurements during concurrent radiation and chemotherapy in glioblastoma will provide information about systemic immune status during treatment. METHODS 16 patients were enrolled in a single-institution, observational, immune surveillance study between 2018 and 2019. Blood was collected prior to starting radiation, and then weekly for a total of 7 timepoints. Plasma was isolated from blood, and cytokine levels were measured with a Luminex 26-cytokine panel. Survival was defined as a binary outcome at two years post-diagnosis: patients living beyond two years were classified as survivors, while those who died within two years were non-survivors. Cytokine levels were compared with a cohort of 8 healthy controls. Data are log2 transformed to reduce skewness. ANOVA was used to find cytokines that differ among 3 groups. Only for those cytokines with significant ANOVA results, pair-wise t-test was performed. RESULTS Increase in IL-34 levels, a proinflammatory cytokine corresponded to a shorter OS. The last measure of pro-inflammatory cytokine IL-12 p70 greater than 1, one month after conclusion of chemotherapy and radiotherapy, corresponded to an increased mortality rate (HR=6.693, p=0.0216). In patients with unmethylated MGMT promoter (<0.79) and a rapid increase in MCP-1, had worse OS (HR=23.69, p=0.0071). DISCUSSION Cytokine levels during chemotherapy and radiation is in glioblastoma are dynamic. We showed previously the immunosuppressive cytokines at baseline predict survival, but increasing proinflammatory cytokine levels were associated with a poor survival. Additional studies may help decode the profoundly immunosuppressive glioblastoma microenvironment.