Myeloid-derived suppressor cells (MDSCs) expansion is a hallmark of cancer. Three major MDSC subsets defined as monocytic (M)-MDSCs, polymorphonuclear (PMN)-MDSCs and early stage (e)MDSCs can be revealed in human diseases. However, the clinical relevance and immunosupressive pattern of these cells in epithelial ovarian cancer (EOC) are unknown. Therefore, we performed a comprehensive analysis of each MDSC subset and immunosupressive factors in the peripheral blood (PB), peritoneal fluid (PF), and the tumor tissue (TT) samples from EOC and integrated this data with the patients' clinicopathological characteristic. MDSCs were analyzed using multicolor flow cytometry. Immunosuppressive factors analysis was performed with ELISA and qRT-PCR. The level of M-MDSCs in the PB/PF/TT of EOC was significantly higher than in healthy donors (HD); frequency of PMN-MDSCs was significantly greater in the TT than in the PB/PF and HD; while the level of eMDSCs was greater in the PB compared with the PF and HD. Elevated abundance of tumor-infiltrating M-MDSCs was associated with advanced stage and high grade of EOC. An analysis of immunosuppressive pattern showed significantly increased blood-circulating ARG/IDO/IL-10-expressing M- and PMN-MDSCs in the EOC patients compared with HD and differences in the accumulation of these subsets in the three tumor immune microenvironments (TIME). This accumulation was positively correlated with levels of TGF-β and ARG1 in the plasma and PF. Low level of blood-circulating and tumor-infiltrating M-MDSCs, but neither PMN-MDSCs nor eMDSCs was strongly associated with prolonged survival in ovarian cancer patients. Our results highlight M-MDSCs as the subset with potential the highest clinical significance.
Ovarian cancer (OC) is usually diagnosed at an advanced stage and is related with poor prognosis. Despite numerous studies, the pathogenesis of OC is still unknown. Recent studies indicate the role of the immune system in the development and spread of OC. The identification of factors and mechanisms involved in that process and their modulation is crucial for creating effective antitumor therapy. We investigated the potential role of Th17 cells in OC patients (n = 71) by analyzing the frequencies of Th17 cells in three different environments, i.e., peripheral blood (PB), peritoneal fluid (PF), and tissue (Th17 infiltrating cells), and the concentration of IL-17A in plasma and PF of patients in terms of their clinical and prognostic significance. Th17 cells were analyzed by flow cytometry as a percentage of CD4+ lymphocytes that expressed intracellular expression of IL-17A. The level of IL-17A in plasma and PF were determined by ELISA. Our results showed accumulation of Th17 cells among tumor-infiltrating CD4+ lymphocytes (p<0.001 in relation to PB). Moreover, the percentage of Th17 cells in both PB and PF of OC patients was significantly lower than that in benign tumors group (n = 35). There were no significant differences in the percentage of Th17 cells in PB, PF, and tissue in relation to clinicopathological characteristics of OC patients and survival. The lower percentage of Th17 cells in the PB and PF of OC patients may promote evasion of host immune response by cancer cells. The concentration of IL-17A in plasma of OC patients was higher (p<0.0001) than that in both benign tumors and control group (n = 10). The PF IL-17A level in OC patients was higher (p<0.0001) than that in women with benign ovarian tumors, indicating its synthesis in OC microenvironment. Higher IL-17A level in PF is correlated with longer (median: 36.5 vs. 27 months) survival of OC patients.
PurposeSubependymal giant cell astrocytoma (SEGA) is a brain tumor associated with tuberous sclerosis complex (TSC). It usually grows in a second decade of life, but may develop in the first months of life. The aim of this work was to establish the incidence, clinical features, and outcome of congenital SEGA in TSC patients.MethodsCohort of 452 TSC patients was reviewed to identify cases with growing or hydrocephalus producing SEGAs in the first 3 months of life. Clinical presentation, size of the tumor, growth rate, mutational analysis, treatment applied, and outcome were analyzed.ResultsTen (2.2 %) patients presented with SEGA in the first 3 months of life. All of them had documented SEGA growth and all developed hydrocephalus. In eight patients, mutational analysis was done, and in all of them, TSC2 gene mutations were identified. Mean maximum SEGA diameter at baseline was 21.8 mm. Mean SEGA growth rate observed postnatally was 2.78 mm per month and tended to be higher (5.43 mm per month) in patients with TSC2/PKD1 mutation than in other cases. Seven patients underwent SEGA surgery and surgery-related complications were observed in 57.1 % cases. One patient was successfully treated with everolimus as a primary treatment.ConclusionsCongenital SEGA develops 2.2 % of TSC patients. Patients with TSC2 mutations, and especially with TSC2/PKD1 mutations, are more prone to develop SEGA earlier in childhood and should be screened for SEGA from birth. In young infants with SEGA, both surgery and mTOR inhibitor should be considered as a treatment option.
The authors report a case of a germinoma of the brain in the child with symptoms restricted to central nervous system. Ten-year-old girl presented initially with sight deterioration, learning difficulties, abnormal behavior, polydipsia, and polyuria. Brain magnetic resonance examination revealed T2 hyperintensity of the corpus callosum, anterior commissure, and caudate nuclei. Brain biopsy revealed extensive macrophage infiltration. Given these results and positive antinuclear antibodies in the blood, immunosuppressive and immunomodulatory treatment was implemented but it was not effective. The patient developed progressive quadriparesis, sleep disturbances, and dementia. Second brain biopsy was performed and it revealed germinoma cells. Chemotherapy was administered, but the girl died due to disseminated intravascular coagulation syndrome. The reported case shows an unusual coexistence of germinoma with prominent inflammation in the brain and highlights the importance of brain biopsy in such complex cases.
PurposeThe aim of the study is to present MRI examinations of the brain and spinal cord, performed in girls with acute severe neurological presentation of paraneoplastic syndrome associated with ovarian teratomas. Paraneoplastic neurological syndrome (PNS) is a rare disorder caused by remote effects of malignancy in different organs. The pathogenesis of PNS concerns the autoimmune system and specific antibodies. PNS can be seen as encephalomyelitis, limbic encephalitis, progressive multifocal leukoencephalopathy, cerebellar ataxia, brainstem encephalitis, and paraneoplastic cerebellar degeneration. These symptoms are potentially reversible, if the underlying neoplasm is removed.MethodsWe presented three girls, aged 13, 17, and 18 years. They were all referred to the hospital because of an acute onset of severe disseminated encephalomyelitis. All MRI exams were performed on a 1.5 T scanner with a routine brain and spinal cord protocol, including TSE T2-WI and FLAIR sequences. In all cases, a contrast agent was injected in the standard dose.ResultsNeurological examination performed at the onset of the disease revealed hemiparesis, seizures, and consciousness disturbances. In one girl, visual field loss was also disclosed. They were all healthy before the onset of the disease. Brain and spinal cord MR imaging revealed multiple hyperintense lesions located supratentorially in the white matter of both hemispheres, in the pons, cerebellum, and spinal cord. Patients were treated with methyloprednisolone IV and IVIG. They all improved but significant sequelae were present. Two of them developed symptoms of acute demyelinating polyradiculoneuropathy within 2 months after the onset of encephalomyelitis. At the same time, brain MRI showed progression of the lesions. In two patients, anti-Yo antibodies were present in blood. Extensive examinations revealed bilateral ovarian teratomas in two patients, and left-sided ovarian teratoma in one case. Surgical resection of teratomas resulted in rapid clinical improvement.ConclusionsThese cases show that in children and adolescents, acute demyelinating disease can be a manifestation of paraneoplastic neurological syndrome. Thus, PNS should always be considered in the differential diagnosis of encephalomyelitis. In female children and adolescents with suspected PNS, it is important to search for ovarian tumours.
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