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Background: Emerging evidence suggests that myeloid cells play a critical role in glioblastoma (GBM) immunosuppression. Disappointing results of recent checkpoint inhibitor trials suggest that combination immunotherapy with alternative agents could be fruitful in overcoming immunosuppression. Overexpression of chemokine receptor CXCR4 is associated with poor prognosis in GBM. We investigate the treatment effects of combination immunotherapy with anti-PD-1 and anti-CXCR4 in a murine glioma model., Methods: C57BL/6 mice were implanted with GL261-Luc+ glioma cells and randomized into 4 arms: (1) control (2) anti-PD-1 (3) anti-CXCR4, and (4) anti-PD-1 and anti-CXCR4 therapy. Overall survival and median survival were assessed. Cell populations were assessed by flow cytometry., Results: Combination therapy conferred a significant survival benefit compared to control and monotherapy arms. Mice that received combination therapy demonstrated immune memory and decreased populations of immunosuppressive tumor-infiltrating leukocytes, such as monocytic myeloid-derived suppressor cells and microglia within the brain. Furthermore, combination therapy improved CD4+/CD8+ ratios in the brain as well as contributed to increased levels of pro-inflammatory cytokines., Conclusions: Anti-CXCR4 and anti-PD-1 combination immunotherapy modulates tumor-infiltrating populations of the glioma microenvironment. Targeting myeloid cells with anti-CXCR4 facilitates anti-PD-1 to promote an antitumor immune response and improved survival rates.

Atypical and anaplastic meningiomas (AAM) are aggressive tumors. This study is aimed at examining associations between patient and tumor-related factors and tumor-related death in patients with AAM. We conducted a population-based cohort study utilizing prospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with diagnosis of AAM from 1973 to 2012 in the SEER database were included. Patients lacking clinical information were excluded. Multivariate analysis between patient and lesion characteristics, and AAM-related death was performed to adjust for confounding factors. We identified and included 522 patients in our study. Mean age at diagnosis was 60.8 ± 15.7 years. The majority of patients were White(73%), 15.5% Black, and 9.8% Asian. Average tumor size was 48.2 ± 20.3 mm. The tumor was locally confined in 57.1%, whereas it had intracranial extension in 29.3%, and extracranial extension in 8.8% of patients. The vast majority (94.8%) of tumors were supratentorial. Gross total resection (GTR) was documented in 65.5% of patients. Age at diagnosis (p = 0.001), tumor size (p = 0.003), surgery result (GTR vs. subtotal resection, p = 0.027), and radiation therapy (p = 0.2) were found to be significantly different between the comparison groups. In a multivariate proportional competing risk regression analysis age (HR 1.03, CI [1.01,1.04], p < 0.001), infratentorial location (HR 2.81, CI [1.20, 6.56], p = 0.017), tumor size (HR 1.01, CI [1.00,1.02], p = 0.032),and radiation treatment (HR 1.52, CI [1.11, 2.09], p = 0.01) were significantly associated with tumor-related death. The association of age at diagnosis, tumor size, location, and radiotherapy with overall survival in patients with AAM is demonstrated. The results provide a context for individualized treatment plans in patients with AAM. Additional studies focusing on issues such as the use of radiation and chemotherapy will clarify the best modality to achieve disease control.

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5-14] and 20 [12-30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.