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Purpose:Upregulation of programmed death-ligand 1 (PD-L1) on circulating and tumor-infiltrating myeloid cells is a critical component of GBM-mediated immunosuppression that has been associated with diminished response to vaccine immunotherapy and poor survival. Although GBM-derived soluble factors have been implicated in myeloid PD-L1 expression, the identity of such factors has remained unknown. This study aimed to identify factors responsible for myeloid PD-L1 upregulation as potential targets for immune modulation.Experimental Design:Conditioned media from patient-derived GBM explant cell cultures was assessed for cytokine expression and utilized to stimulate naïve myeloid cells. Myeloid PD-L1 induction was quantified by flow cytometry. Candidate cytokines correlated with PD-L1 induction were evaluated in tumor sections and plasma for relationships with survival and myeloid PD-L1 expression. The role of identified cytokines on immunosuppression and survival was investigated in vivo utilizing immunocompetent C57BL/6 mice bearing syngeneic GL261 and CT-2A tumors.Results:GBM-derived IL6 was identified as a cytokine that is necessary and sufficient for myeloid PD-L1 induction in GBM through a STAT3-dependent mechanism. Inhibition of IL6 signaling in orthotopic murine glioma models was associated with reduced myeloid PD-L1 expression, diminished tumor growth, and increased survival. The therapeutic benefit of anti-IL6 therapy proved to be CD8+ T-cell dependent, and the antitumor activity was additive with that provided by programmed death-1 (PD-1)-targeted immunotherapy.Conclusions:Our findings suggest that disruption of IL6 signaling in GBM reduces local and systemic myeloid-driven immunosuppression and enhances immune-mediated antitumor responses against GBM.

Methods pertaining to experiments presented as supplementary figures.

Supplementary Tables S1-S4.

Supplementary Figures S1-S7.

Spine surgery has evolved from the advent of imaging and navigation guidance, particularly with the rise of robotic surgical assistance. Navigation guidance has demonstrated potential for increased accuracy of transpedicular screw placement and resecting primary and metastatic spinal tumors. Robotic surgery is widely accepted in other surgical fields because laparoscopic techniques applied to robots can increase operator dexterity and improve visualization. Robotic assistance with spinal tumors has enjoyed rising interest owing to the potential for safe and minimally traumatic resection. We discuss available robots used for navigation-guided transpedicular screw placement and state-of-the-art robotic techniques for spinal or paraspinal tumor resection.

Purpose: Upregulation of programmed death-ligand 1 (PD-L1) on circulating and tumor-infiltrating myeloid cells is a critical component of GBM-mediated immunosuppression that has been associated with diminished response to vaccine immunotherapy and poor survival. Although GBM-derived soluble factors have been implicated in myeloid PD-L1 expression, the identity of such factors has remained unknown. This study aimed to identify factors responsible for myeloid PD-L1 upregulation as potential targets for immune modulation. Experimental Design: Conditioned media from patient-derived GBM explant cell cultures was assessed for cytokine expression and utilized to stimulate naïve myeloid cells. Myeloid PD-L1 induction was quantified by flow cytometry. Candidate cytokines correlated with PD-L1 induction were evaluated in tumor sections and plasma for relationships with survival and myeloid PD-L1 expression. The role of identified cytokines on immunosuppression and survival was investigated in vivo utilizing immunocompetent C57BL/6 mice bearing syngeneic GL261 and CT-2A tumors. Results: GBM-derived IL6 was identified as a cytokine that is necessary and sufficient for myeloid PD-L1 induction in GBM through a STAT3-dependent mechanism. Inhibition of IL6 signaling in orthotopic murine glioma models was associated with reduced myeloid PD-L1 expression, diminished tumor growth, and increased survival. The therapeutic benefit of anti-IL6 therapy proved to be CD8+ T-cell dependent, and the antitumor activity was additive with that provided by programmed death-1 (PD-1)-targeted immunotherapy. Conclusions: Our findings suggest that disruption of IL6 signaling in GBM reduces local and systemic myeloid-driven immunosuppression and enhances immune-mediated antitumor responses against GBM.

Given the rarity of intracranial plasmacytomas, these lesions are frequently misdiagnosed as pituitary adenomas. We report on the distinguishing characteristics of sellar plasmacytomas from cases in the literature and our experience. A literature search was conducted to collect all documented cases of a plasmacytoma originating in the sellar region. Patient characteristics, medical history, presentation, tumor characteristics, and survival data were collected. An additional case from our institution not previously reported was included. Thirty-one patients with sellar plasmacytomas were studied. Presenting symptoms were most commonly headache (68%), diplopia (65%) and visual field disturbances (10%). Fifteen patients (48%) were initially suspected of having a pituitary adenoma. Pathologic diagnosis of plasmacytoma preceded a finding of multiple myeloma in 14 cases (45%). Thirty patients (90%) had surgical intervention. Adjuvant therapy consisted of radiotherapy for twenty-five patients (81%) and chemotherapy for sixteen (52%). Tumor recurrence was reported for 7 cases (23%). Nine deaths were reported (23%). We demonstrate that cranial nerve involvement is far more common in sellar plasmacytomas than conventional pituitary adenomas. Given the successful management of these tumors with radiotherapy, such deficits, particularly in patients with known multiple myeloma, should impact the diagnostic workup and treatment considerations.

Malignant astrocytomas constitute the most aggressive and common primary tumors of the central nervous system. The standard treatment protocol for these tumors involves maximum safe surgical resection with adjuvant chemoradiotherapy. Despite numerous advances in surgical techniques and adjuncts, as well as the ongoing renaissance in the genetic and molecular characterization of these tumors, malignant astrocytomas continue to be associated with poor prognosis, with median overall survival averaging 15 months for grade IV astrocytomas after standard-of-care treatment. In this article, the goals, principles, techniques, prognostic factors, and modern outcomes of malignant astrocytoma surgery are reviewed. Particular attention is paid to contemporary methods of neuronavigation and functional mapping, the prognostic significance of the extent of resection, surgically delivered adjunctive therapies, and future avenues of research.

Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response.