Primary CNS Tumors Research Articles

The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors

abstractAim of the study: Astrocytomas are primary CNS malignancies which infiltrate the peritumoral tissue, even when they are low-grade. Schwannomas are also primary CNS tumors, however, they do not show peritumoral infiltration similarly to brain metastases which almost never invade the neighboring parts of brain. Extracellular matrix is altered in composition in various cancer types and is proposed to play an important role in the development of invasiveness of astrocytic tumors. This study aims to identify differences in the ECM composition of CNS tumors with different invasiveness.Materials and methods: The mRNA and protein levels of ECM components were measured by QRT-PCR and mass-spectrometry, respectively, in grade II astrocytoma, NSCLC brain metastasis, schwannomas, and non-tumor brain control samples. Expressional data was analyzed statistically with ANOVA and nearest neighbor search.Results: There is a significant difference in the expressional pattern of invasion-related ECM components among various CNS tumors, especially among those of different embryonic origin. Non-invasive tumors show only slight differences in the expressional pattern of ECM molecules. Tumor samples can be separated based on their expressional pattern using statistical classifiers, therefore the ECM composition seems to be typical of various cancer types.Conclusions: Differences in the expressional pattern of the ECM could be responsible for the different invasiveness of various CNS tumors.

B - 16Neuropsychological Functioning of Early Childhood Left Temporal Primary CNS Neoplasm Status-Post Resection: Evidence for the “Crowding Out” Hypothesis

B - 16Neuropsychological Functioning of Early Childhood Left Temporal Primary CNS Neoplasm Status-Post Resection: Evidence for the “Crowding Out” Hypothesis

Meningioma da Fossa Craniana Anterior Associado a Depressão

Introdução: Meningiomas intracranianos correspondem a 20% dos tumores primários do sistema nervoso central. A localização frontobasal ocorre entre 8% a 15% dos casos. Pode apresentar como manifestação clínica inicial a síndrome de Foster Kennedy (anosmia, atrofia ótica homolateral e papiledema contralateral), transtorno de comportamento por acometimento do lobo frontal (apatia, abulia, depressão), incontinência urinária e crises convulsivas. Relato do caso: Paciente feminino de 49 anos, em tratamento ambulatorial de depressão há quatro anos. Resultado: Exame de ressonância magnética revelou lesão expansiva frontobasal bilateral. Submetida a exérese total da lesão que revelou meningioma meningotelial. Conclusão: As lesões do lobo frontal provocam alterações da personalidade e distúrbios emocionais, o que pode ocasionar um diagnóstico errôneo e tratamento inadequado antes de conhecer a sua verdadeira causa.

GP.05 The risk of malignancy after stereotactic radiosurgery

Background: A major concern of patients undergoing Gamma Knife radiosurgery (GKS) for benign tumors and other conditions is the risk of a separate secondary malignancy or malignant -transformation. The incidence of radiosurgery-associated malignancy based on long-term follow-up remains unknown. Methods: We conducted a population-based cohort study to estimate the incidence rate of both malignant transformation and a separate radiation-associated malignancy in patients undergoing GKS from 1987 to 2016 at 5 centers. Results: 11 527 patients underwent radiosurgery for meningioma (n=3261), arteriovenous malformation (n=2868), trigeminal neuralgia (n=1982), vestibular schwannoma (n=1957), pituitary adenoma (n=1193), other (n=266). The follow-up time ranged from 0.3 to 23.8 years. Four cases of malignant transformation and 3 new malignant brain tumors were reported, two of which were not within the irradiated field. The incidence of malignant transformation was 6.6 per 100 000 patient-years and of new malignancy, either locally or distant, was 5 in 100 000 patient-years. These risks are not higher than the Central Brain Tumor Registry of the United States derived annual incidence rate of all primary malignant CNS tumors of 7.15 per 100 000. Conclusions: Physicians can safely counsel patients that the risk of malignancy after stereotactic radiosurgery remains extremely low, even at long-term follow-up of greater than 10 years.

P.034 Supratentorial lateral ventricle hemangioblastoma in Von Hippel Lindau

Background: Supratentorial ventricular hemangioblastoma (HB) associated with Von Hippel Lindau (VHL) are extremely rare. Due to their vascularity and location, their management can be difficult. Methods: A 35 year old female with VHL, has been followed for 25 years with multiple intracranial and spinal tumours. Surgical removal was carried out on one large cystic and solid posterior fossa lesion. In addition, she underwent adrenalectomy for pheochromocytoma. There were no pancreatic or renal lesions. On serial follow up for years, a left frontal ventricular lesion showed increasing size with clinical signs of increased ICP and marked hydrocephalus, requiring shunting procedures, which were carried out 11 years ago. She has been clinically stable since. Results: Hemangioblastomas of the CNS are rare and account for 2% of primary CNS tumours. Supratentorial location is estimated at 4% for sporadic and 13% for HB associated with VHL. The lateral ventricular location is extremely rare. Review of the literature revealed a total of 9 cases of supratentorial ventricular location. The majority of the lesions are associated with VHL and they are solid and vascular lesions. In our cases there was a cystic component. Conclusions: If removal is contemplated, angiography with possible preoperative embolization may be required.

Phase I study of afatinib and radiotherapy (RT) with or without temozolomide (TMZ) in newly diagnosed glioblastoma (GB).

2036Background: GB is a malignant primary incurable CNS tumor with poor prognosis. RT + TMZ is standard treatment for newly diagnosed GB suitable for radical treatment. ErbB pathway dysregulation h...

The incidence of germline cancer susceptibility mutations in primary CNS neoplasm patients.

1586Background: Genomic profiling is performed on primary brain (CNS) tumors to identify somatic mutations. Several syndromes, (e.g. Neurofibromatosis) are well known causes of CNS neoplasms but da...

Patterns of care and outcomes for glioblastoma in patients with poor performance status.

e14093Background: Glioblastoma (GBM) is the most common and aggressive primary CNS tumor with dismal survival outcomes. The treatment with tumor resection followed by chemoradiation is generally th...

Pericytes/vessel-associated mural cells (VAMCs) are the major source of key epithelial-mesenchymal transition (EMT) factors SLUG and TWIST in human glioma.

Epithelial-to-mesenchymal transition (EMT) is supposed to be responsible for increased invasion and metastases in epithelial cancer cells. The activation of EMT genes has further been proposed to be important in the process of malignant transformation of primary CNS tumors. Since the cellular source and clinical impact of EMT factors in primary CNS tumors still remain unclear, we aimed at deciphering their distribution in vivo and clinico-pathological relevance in human gliomas.We investigated 350 glioma patients for the expression of the key EMT factors SLUG and TWIST by immunohistochemistry and immunofluorescence related to morpho-genetic alterations such as EGFR-amplification, IDH-1 (R132H) mutation and 1p/19q LOH. Furthermore, transcriptional cluster and survival analyses were performed.Our data illustrate that SLUG and TWIST are overexpressed in gliomas showing vascular proliferation such as pilocytic astrocytomas and glioblastomas. EMT factors are exclusively expressed by non-neoplastic pericytes/vessel-associated mural cells (VAMCs). They are not associated with patient survival but correlate with pericytic/VAMC genes in glioblastoma cluster analysis.In summary, the upregulation of EMT genes in pilocytic astrocytomas and glioblastomas reflects the level of activation of pericytes/VAMCs in newly formed blood vessels. Our results underscore that the negative prognostic potential of the EMT signature in the group of diffuse gliomas of WHO grade II-IV does most likely not derive from glioma cells but rather reflects the degree of proliferating mural cells thereby constituting a potential target for future alternative treatment approaches.

Distinct demographic profile and molecular markers of primary CNS tumor in 1873 adolescent and young adult patient population

We present detailed demographic profile, tumor types, and their molecular markers in adolescent and young adult (AYA) patients of age group between 15 and 39years with primary central nervous system (PCNS) tumors, and compare with pediatric and adult patient populations. Demographic- and disease-related information of 1873 PCNS tumor patients of age 15-39years registered between 1 January 2011 and 31 December 2015 at our institution was analyzed with respect to their demographics and tumor subtypes. Various molecular markers for glial tumors and subgroup classification of medulloblastoma were evaluated for AYA, pediatric, and older adult patient populations. AYA constituted 27% of all PCNS. Median age was 29years. Glial tumors (62.36%) comprised the largest tumor type with astrocytoma (38.55%) being the most common histology. Glioblastoma (51.52%) was the commonest astrocytic tumor with 74.67% of them being isocitrate dehydrogenase 1 (IDH1) negative and 41.38% with O (6)-methylguanine DNA methyltransferase (MGMT) promoter methylated. Diffuse astrocytoma and glioblastoma showed significantly higher IDH1 positivity and loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) for AYAs as compared to pediatric and adult patient populations (p < 0.0001). Medulloblastoma (73.8%) was the most commonly diagnosed embryonal tumor, with sonic hedgehog (SHH) being the commonest molecular subtype (48%). Younger patients among AYA population presents with pediatric type of tumor spectrum, while older ones present with more aggressive tumor subtypes. This is among the few studies reporting spectrum of PCNS tumor in AYA population with distinct tumor subtypes and molecular profiles. AYA patient populations may need special attention with appropriately designed clinical trials.

Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas from 1995 – 2013. (P6.143)

Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas from 1995 – 2013. (P6.143)

Quality improvement in neurology: Neuro-oncology quality measurement set.

Over 78,000 new CNS tumors are diagnosed each year in the United States, nearly one-third of which are primary malignant brain tumors,1 and the US prevalence of primary brain tumors is approximately 688,000.2 While primary CNS neoplasms represent only 1.4% of new cancer diagnoses, approximately 2.7% of cancer deaths are related to CNS neoplasms,3 and it is estimated that 16,947 deaths will result from primary CNS tumors in 2017.1 Population-based studies have shown that socioeconomic disparities are present within the neuro-oncology community,4–7 highlighting the need for a unified system of quality metrics in this growing field. Toward this end, several authors have published work on quality-based practice and on the inclusion of patient-reported outcomes in brain tumor care.8–12

The 2016 WHO classification of primary central nervous system tumors: a clinician's view

This article is devoted to the latest edition of the 2016 WHO classification of primary CNS tumors. The authors, who are clinicians and not morphologists, have tried to analyze and briefly present the main changes to the new edition of the WHO classification of primary CNS tumors, the main difference of which from the previous 2007 classification is inclusion of the molecular genetic features of primary CNS tumors in the classification criteria. The article focuses mainly on the classification issues of diffuse gliomas and glioblastoma, with assessment of the role of IDH-1,2, ATRX, TERT, and MGMT mutations as well as a 1p/19q co-deletion. The article briefly describes some new nosological forms (e.g., Grade III anaplastic pleomorphic xanthoastrocytoma) and presents a new approach to the classification of embryonic (medulloblastoma) and glial childhood tumors as well as tables of the main differences between 2016 and 2007 WHO classifications of primary CNS tumors. Based on their own clinical experience, the authors dispute with the described classification and suggest their own ideas for improving the classification of primary CNS tumors in the future.

Predictors of clinical outcome in pediatric oligodendroglioma: meta-analysis of individual patient data and multiple imputation.

OBJECTIVE Oligodendroglioma is a rare primary CNS neoplasm in the pediatric population, and only a limited number of studies in the literature have characterized this entity. Existing studies are limited by small sample sizes and discrepant interstudy findings in identified prognostic factors. In the present study, the authors aimed to increase the statistical power in evaluating for potential prognostic factors of pediatric oligodendrogliomas and sought to reconcile the discrepant findings present among existing studies by performing an individual-patient-data (IPD) meta-analysis and using multiple imputation to address data not directly available from existing studies. METHODS A systematic search was performed, and all studies found to be related to pediatric oligodendrogliomas and associated outcomes were screened for inclusion. Each study was searched for specific demographic and clinical characteristics of each patient and the duration of event-free survival (EFS) and overall survival (OS). Given that certain demographic and clinical information of each patient was not available within all studies, a multivariable imputation via chained equations model was used to impute missing data after the mechanism of missing data was determined. The primary end points of interest were hazard ratios for EFS and OS, as calculated by the Cox proportional-hazards model. Both univariate and multivariate analyses were performed. The multivariate model was adjusted for age, sex, tumor grade, mixed pathologies, extent of resection, chemotherapy, radiation therapy, tumor location, and initial presentation. A p value of less than 0.05 was considered statistically significant. RESULTS A systematic search identified 24 studies with both time-to-event and IPD characteristics available, and a total of 237 individual cases were available for analysis. A median of 19.4% of the values among clinical, demographic, and outcome variables in the compiled 237 cases were missing. Multivariate Cox regression analysis revealed subtotal resection (p = 0.007 [EFS] and 0.043 [OS]), initial presentation of headache (p = 0.006 [EFS] and 0.004 [OS]), mixed pathologies (p = 0.005 [EFS] and 0.049 [OS]), and location of the tumor in the parietal lobe (p = 0.044 [EFS] and 0.030 [OS]) to be significant predictors of tumor progression or recurrence and death. CONCLUSIONS The use of IPD meta-analysis provides a valuable means for increasing statistical power in investigations of disease entities with a very low incidence. Missing data are common in research, and multiple imputation is a flexible and valid approach for addressing this issue, when it is used conscientiously. Undergoing subtotal resection, having a parietal tumor, having tumors with mixed pathologies, and suffering headaches at the time of diagnosis portended a poorer prognosis in pediatric patients with oligodendroglioma.

TMIC-01. ALERTING THE IMMUNE SYSTEM BY REMOVING EPIGENETIC SILENCING OF TH1 CHEMOKINES

Solid tumors employ multiple mechanisms to evade immunologic detection and destruction. However, the potential to enhance the immune response to cancer has been proven in several malignancies and is under investigation in many others, including primary CNS tumors. Brain tumors, in particular, lack robust T-cell infiltration, suggesting poor immune surveillance. Recent studies have found that tumor cells express T-cell attracting chemokines, CXCL9/10, in response to interferon gamma (IFNg). Chemokine expression can be further amplified by drugs that prevent epigenetic silencing, such as histone methyltransferase inhibitors or histone deacetylase (HDAC) inhibitors. This approach increases T-cell trafficking to tumors in vivo and enhances the anti-tumor efficacy of checkpoint blockade. We hypothesized that T-cell trafficking to brain tumors could be increased by epigenetically enhancing CXCL9/10 expression. Assays were performed on human glioma brain tumor cell lines. CXCL9/10 expression were measured by real-time PCR and Western blot. GSK126, a commercially available methyltransferase inhibitor, was utilized to demethylate histone H3 (K9/K27). LB201 (Lixte Biotechnology, Setatuket, NY) was used to inhibit class 1/2 HDAC. Histone methylation and acetylation status were examined using Western blot analysis. T-cell migration was measured using transwell migration assays. expression of CXCL9/10 was induced by IFNg in brain tumor lines. Chemokine expression was further increased when cells were treated with GSK126 and LB201 compared to IFNg alone. Migration assays confirmed that tumor cells treated with GSK126 and LB201 released T-cell chemotactic factors that increased T-cell migration. These studies demonstrate that brain tumors express T-cell attracting chemokines CXCL9/10 in response to IFNg. Further, GSK126 and the combination of GSK126 and LB201 enhanced expression of CXCL9/10, resulting in increased T-cell migration toward tumor cells. Together, these data provide a potential means to enhance the efficacy of immune therapies for brain tumors by promoting T-cell trafficking toward tumor cells.

Clinical and Genetic Risk Prediction of Subsequent CNS Tumors in Survivors of Childhood Cancer: A Report From the COG ALTE03N1 Study.

Purpose Survivors of childhood cancer treated with cranial radiation therapy are at risk for subsequent CNS tumors. However, significant interindividual variability in risk suggests a role for genetic susceptibility and provides an opportunity to identify survivors of childhood cancer at increased risk for these tumors. Methods We curated candidate genetic variants from previously published studies in adult-onset primary CNS tumors and replicated these in survivors of childhood cancer with and without subsequent CNS tumors (82 participants and 228 matched controls). We developed prediction models to identify survivors at high or low risk for subsequent CNS tumors and validated these models in an independent matched case-control sample (25 participants and 54 controls). Results We demonstrated an association between six previously published single nucleotide polymorphisms (rs15869 [ BRCA2], rs1805389 [ LIG4], rs8079544 [ TP53], rs25489 [ XRCC1], rs1673041 [ POLD1], and rs11615 [ ERCC1]) and subsequent CNS tumors in survivors of childhood cancer. Including genetic variants in a Final Model containing age at primary cancer, sex, and cranial radiation therapy dose yielded an area under the curve of 0.81 (95% CI, 0.76 to 0.86), which was superior ( P = .002) to the Clinical Model (area under the curve, 0.73; 95% CI, 0.66 to 0.80). The prediction model was successfully validated. The sensitivity and specificity of predicting survivors of childhood cancer at highest or lowest risk of subsequent CNS tumors was 87.5% and 83.5%, respectively. Conclusion It is possible to identify survivors of childhood cancer at high or low risk for subsequent CNS tumors on the basis of genetic and clinical information. This information can be used to inform surveillance for early detection of subsequent CNS tumors.

Recent Advances in the Classification and Treatment of Ependymomas.

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

Haematological outcome of concomitant chemoradiation with Temozolomide (CCRT) versus radiation therapy (RT) alone in patients with high grade gliomas

High grade gliomas(HGG) are the most common primary CNS tumors in adult. Even with multidisciplinary approach, the outcome is miserable. However recently concomitant chemoradiation (CCRT) with temozolomide has been effectively used with increase in median survival &amp; good clinical outcome. This quasi experimental study was done in the department of Radiation Oncology in National Institute of Cancer Research &amp; Hospital ( NICRH) Mohakhali , Dhaka during January 2014 to December 2014. Sixty patients with newly diagnosed &amp; histologically proved high grade glioma were assigned to receive either radiation therapy alone (fractionated focal irradiation in daily fractions of 2 Gy in five fractions per week for six weeks, for a total 60 Gy) or radiation therapy plus Temozolomide( 75 mg/m2 from 1st day of radiation therapy to last day of radiation therapy) followed by six cycles of adjuvant temozolomide (150 to 200mg per square meter for five days during each 28 day cycle). Haematological abnormalities and neurotoxicities were compared between the patients of two arms. Patients treated CCRT showed more toxicities than the radiation therapy alone in some stages. As a whole the differences were not statistically significant.Bangladesh Med J. 2016 Sep; 45 (3): 126-130

Abstract CT030: STARTRK-NG: A phase 1/1b study of entrectinib in children and adolescents with advanced solid tumors and primary CNS tumors, with or without TRK, ROS1, or ALK fusions

Abstract Background: The STARTRK-NG (Studies of Tumor Alterations Responsive to Targeting Receptor Kinases - Next Generation) trial is a Phase 1/1b dose-escalation and expansion study of entrectinib in pediatric patients with cancer. Entrectinib is a potent oral, CNS-penetrant, inhibitor of the tyrosine kinases TRKA/B/C (encoded by the genes NTRK1/2/3, respectively), ROS1, and ALK with IC50s &amp;lt; 2 nM (biochemical kinase assay). Three adult studies (Phase 1 ALKA-372-001, Phase 1 STARTRK-1, and Phase 2 STARTRK-2) have enrolled hundreds of patients with advanced or metastatic solid tumors harboring TRKA/B/C, ROS1, or ALK molecular alterations, with or without CNS disease. Previously, we reported 400 mg/m2 daily as the adult body surface area (BSA)-based Recommended Phase 2 Dose (RP2D) (Patel et al, ASCO 2015). An objective response rate of 79% was seen in 24 tyrosine kinase inhibitor-naïve patients with TRK, ROS1, or ALK fusions who were treated at doses consistent with the RP2D (Drilon et al, AACR 2016). Gene fusions have been observed in a variety of adult solid tumor types, including non-small cell lung cancer, salivary gland cancers, soft tissue sarcomas and glioneuronal tumors. These fusions have also been found in cancers that affect the pediatric population, such as infantile fibrosarcoma, juvenile breast cancer, mesoblastic nephroma, intrinsic pontine gliomas, acute leukemias and anaplastic lymphoma. In addition, overexpression of TRKB and activating ALK point mutations have been observed in neuroblastoma. Thus, a pan-TRK, ROS1, and ALK inhibitor, like entrectinib, may potentially have broad therapeutic utility in pediatric patients. Methods: This is a multicenter, dose escalation study in pediatric patients (aged 2-21 years) with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 1b) in patients with primary brain tumors harboring TRK, ROS1, or ALK molecular alterations inclusive of gene fusions, neuroblastoma, and other non-neuroblastoma, extracranial solid tumors harboring TRK, ROS1, or ALK gene fusions (NCT02650401). During dose escalation, a 3+3 schema will be used to determine the pediatric RP2D of entrectinib with a starting dose of 250 mg/m2 (approximately 60% of the adult BSA-based RP2D), administered orally once daily in repeated 4-week cycles, with concordant pharmacokinetics and pharmacodynamics studies. Up to four dose levels will be evaluated. Dose modifications, if necessary, will follow a protocol-specific dosing nomogram for each dose level. Once the pediatric RP2D is determined, the Phase 1b expansion cohorts will be opened simultaneously, and prospective molecular profiling will be performed to determine eligibility except for patients with neuroblastoma. Citation Format: Ami V. Desai, Garrett M. Brodeur, Jennifer Foster, Suzanne Shusterman, Amit J. Sabnis, Magaret Macy, Cynthia Wetmore, Ellen Basu, Zachary Hornby, Vanessa Esquibel, Edna Chow Maneval, Pratik S. Multani, Elizabeth Fox. STARTRK-NG: A phase 1/1b study of entrectinib in children and adolescents with advanced solid tumors and primary CNS tumors, with or without TRK, ROS1, or ALK fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT030. doi:10.1158/1538-7445.AM2017-CT030

Abstract 3998: Alerting the immune system by removing epigenetic silencing of Th1 chemokines

Abstract BACKGROUND: Solid tumors employ multiple mechanisms to evade an immune response. However, the potential to enhance the immune response to cancer has been proven in several malignancie and is under investigation in many others, including primary CNS tumors. Brain tumors in particular lack robust T-cell infiltration. Recent studies have found that certain tumors can be induced to express T-cell attracting chemokines, CXCL9 and CXCL10, by interferon gamma (IFNg). This response is further amplified using methyltransferase inhibitors (Peng, et al. Nature 2015. Vol 527: 249-253.), resulting in increased Tcell trafficking to tumors both in vitro and in vivo. We hypothesized that T-cell trafficking to brain tumors could likewise be enhanced with DNA and histone methyltransferase inhibitors to induce CXCL9 and CXCL10 transcription. METHODS: Assays were performed on 7 human glioma brain tumor cell lines. CXCL9 and CXCL10 expression were measured by real-time PCR. Two commercially available methyltransferase inhibitors, 5-AZA-dC and GSK126, were utilized to demethylate DNA and histone H3 (K9 and K27), respectively. Histone methylation status was examined using Western blot. T-cell migration was measured using transwell migration assays. RESULTS: IFNg increased CXCL9 and CXCL10 transcription in brain tumor lines. GSK126 and 5-AZA-dC enhanced expression of CXCL9 and CXCL10 compared to IFNg alone. Migration assays confirmed T-cell trafficking towards chemokines produced by tumor cells in response to methyltransferase inhibitors. CONCLUSIONS: These studies demonstrate that brain tumors express T-cell attracting chemokines CXCL9 and CXCL10 in response to IFNg. Further, GSK126 and the combination of GSK126 and 5-AZA-dC enhanced expression of CXCL9 and CXCL10 transcription by real-time PCR and T-cell trafficking by migration assay. Together, these data provide a potential means to increase T-cell trafficking into tumors and potentially enhances the efficacy of immune therapies for brain tumors. Citation Format: Heather M. Sonnemann, Amber J. Giles, Caitlin M. Reid, Marsha-Kay N. Hutchinson, Deric M. Park, Mark R. Gilbert. Alerting the immune system by removing epigenetic silencing of Th1 chemokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3998. doi:10.1158/1538-7445.AM2017-3998