BackgroundImmunotherapeutic approaches, such as dendritic cell (DC) vaccination, have emerged as promising strategies in the treatment of glioblastoma. Despite their promise, however, the absence of objective biomarkers and/or immunological monitoring techniques to assess the clinical efficacy of immunotherapy still remains a primary limitation. To address this, we sought to identify a functional biomarker for anti-tumor immune responsiveness associated with extended survival in glioblastoma patients undergoing DC vaccination.Methods28 patients were enrolled and treated in two different Phase 1 DC vaccination clinical trials at UCLA. To assess the anti-tumor immune response elicited by therapy, we studied the functional responsiveness of pre- and post-vaccination peripheral blood lymphocytes (PBLs) to the immunostimulatory cytokines interferon-gamma (IFN-γ) and interleukin-2 (IL-2) in 21 of these patients for whom we had adequate material. Immune responsiveness was quantified by measuring downstream phosphorylation events of the transcription factors, STAT-1 and STAT-5, via phospho-specific flow cytometry.ResultsDC vaccination induced a significant decrease in the half-maximal concentration (EC-50) of IL-2 required to upregulate pSTAT-5 specifically in CD3+CD8+ T lymphocytes (p < 0.045). Extended survival was also associated with an increased per cell phosphorylation of STAT-5 in cytotoxic T-cells following IL-2 stimulation when the median post/pre pSTAT-5 ratio was used to dichotomize the patients (p = 0.0015, log-rank survival; hazard ratio = 0.1834, p = 0.018). Patients whose survival was longer than two years had a significantly greater pSTAT-5 ratio (p = 0.015), but, contrary to our expectations, a significantly lower pSTAT-1 ratio (p = 0.038).ConclusionsOur results suggest that monitoring the pSTAT signaling changes in PBL may provide a functional immune monitoring measure predictive of clinical efficacy in DC-vaccinated patients.

These results reveal an innovative, clinically feasible strategy for the treatment of glioblastoma.

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Background:Saccrococcygeal teratomas (SCT) are derived from embryonic germ cell layers. They frequently present at the base of the coccyx within the pelvis. While these tumors are common in children, they are exceedingly rare in adults. In adults, a majority of these tumors are intrapelvic and associated with a low risk of malignant transformation. Therefore, this contributes to a good prognosis following resection of mostly benign lesions.Case Description:An adult female with chronic pelvic pain presented with a sacral teratoma. She failed conservative treatment and underwent a coccygectomy with an en-bloc excision of the tumor. Microscopic histological analysis showed no evidence of immature or malignant elements, confirming the diagnosis of a mature, benign, cystic SCT.Conclusions:Mature SCTs in adults are rare malignant lesions. In this case, the patient was cured following primary surgical excision requiring en-bloc coccygectomy.

Background:Ependymomas are relatively uncommon tumors that constitute about 7% of all primary intracranial neoplasms. Among these, high-grade ependymomas are locally aggressive and recur most commonly at the primary site following resection. Ependymomas are also known to be the one glial neoplasm that tends to frequently metastasize inside and outside the central nervous system (CNS) that complicates workup and management. Metastasis due to surgical manipulation is common and neurosurgeons should be well-versed in the most effective methods to remove these tumors in order to avoid such metastases.Case Description:Here, we report a case of a 28-year-old female who initially presented with a parenchymal World Health Organization (WHO) grade III anaplastic ependymoma of the occipital lobe without metastasis. After multiple resections, the patient showed no evidence of disease recurrence for 2 years. During follow-up, new metastasis to the frontal lobe as well as to the lung were discovered 2 years after the initial surgery, without recurrence at the tumor's primary site.Conclusions:While uncommon, this case demonstrates the possibility for ependymomas to metastasize via cerebrospinal fluid to other locations within the CNS and hematologically to extraneural locations without recurring locally.