bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-34. NL-201, A DE NOVO ENGINEERED IL2 MIMETIC, SYNERGIZES WITH RADIOTHERAPY TO GENERATE POTENT ANTITUMOR ACTIVITY IN PRECLINICAL GLIOBLASTOMA MODELS
Authors: Huntoon Kristin , Lee DaeYong , Lu Yifei , Gallup Thomas , Jiang Wen , Kim Betty 
Published: November 2022

Abstract
Combining radiotherapy (RT), a standard of care treatment for many cancer types, with immunotherapeutic agents has been gaining interest due to improved efficacy. One such approach is RT in combination with high-dose recombinant interleukin 2 (IL-2), which elicits anti-tumor immune responses by stimulating T-cell and NK cell populations. Although effective for some patients, the overall clinical benefit of recombinant IL-2 is limited by toxicity at high doses and the expansion of regulatory T cells (Tregs) at low doses, effects thought to be mediated by preferential binding to IL2Rα (i.e. CD25). In this study we examined RT in combination with NL-201, a highly potent and stable CD25-independent IL-2/IL-15 agonist with enhanced affinity for the IL-2Rβγ heterodimeric receptor. Single-agent NL-201 was well tolerated in mice, yielded tumoricidal activity, expanded peripheral T cells, and enhanced the infiltration of effector T cells and dendritic cells (DCs) into murine glioblastoma (GL261 and SB28). In combination with RT, NL-201 enhanced activation of the cytosolic DNA sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in increased type I interferon (IFN) production in DCs and, consequently, greater tumor infiltration by T cells and more efficient priming of antigen-specific T cells by professional antigen presenting cells (APCs). The immune stimulatory mechanisms triggered by the NL-201 and RT combination resulted in superior tumor growth inhibition. We demonstrated that the CD25-independent IL-2 and IL-15 receptor agonist, NL-201, in combination with RT is well-tolerated and elicits robust anti-tumor activity through both innate and adaptive responses, including in checkpoint resistant tumors. Furthermore, we identify a unique mechanism in which NL-201 synergizes with RT. Taken together, the results provided herein support further preclinical and clinical investigation of this novel combination regimen.
IMMU-37. ANTI-CD47 TREATMENT POTENTIATES PHAGOCYTOSIS OF MEDULLOBLASTOMA BY M1 POLARIZED MACROPHAGES FOLLOWING IRRADIATION
Authors: Gamboa Nicholas , Baker Cordell , Youssef Osama , Cheshier Samuel 
Published: November 2022

Abstract
Medulloblastoma (MB) is the most common malignant brain tumor of childhood and accounts for 15–20% of all pediatric brain tumors. Despite significant advancements over the last decade in our understanding of the molecular underpinnings of MB, the overall risk of recurrence remains high, prognosis remains poor, and available treatment modalities remain limited for patients with this disease. Accordingly, the area of targeting tumor immune resistance has garnered increasing interest as a potentially safe and effective adjunctive therapy. CD47 is a cell surface protein that acts as a primary “don’t eat me” signal to the innate immune system and has been shown to be crucial in allowing tumor cells to evade phagocytosis by tumor-associated macrophages. Several preclinical studies aimed at blocking this “don’t eat me signal” through the application of a mouse anti-human monoclonal antibody (Ab) to CD47 (anti-CD47) have shown promise in pediatric brain tumor models. Further, chemotherapy and irradiation have been shown to increase the expression of pro-phagocytic signals on the surfaces of tumor cells. The authors examined the use of anti-CD47 Ab on the rates of phagocytosis of MB cells undergoing different single-fraction doses of external beam irradiation in vitro. The use of anti-CD47 Ab in the D425 MB cell line phagocytosis assay significantly increased rates of phagocytosis for 0 Gy (4.1% without vs. 20.3% with anti-CD47 Ab; p &lt; 0.0001), 2 Gy (7.4% without vs. 23.4% with anti-CD47 Ab; p &lt; 0.0001), 5 Gy (11.9% without vs. 27.3% with anti-CD47 Ab; p &lt; 0.0001), 10 Gy (21.7% without vs. 34% with anti-CD47 Ab; p &lt; 0.0001), and 20 Gy treatment groups (27.2% without vs. 43.9% with anti-CD47 Ab; p &lt; 0.0001). A similar pattern of phagocytosis potentiation through use of anti-CD47 Ab with increasing doses of radiation was seen in D458 and D341 MB cell lines.
IMMU-40. KINETICS OF DEXAMETHASONE-INDUCED ALTERATIONS OF DIVERSE IMMUNE SUBSETS IN VIVO
Authors: Yaghi Nasser , Watanabe Masashi , Watowich Matthew , Li Aiguo , Briceno Nicole , Yaghi Omar , Livak Ferenc , Siddiqui Shafiuddin , Wolcott Karen , Zhang Wei , Zhang Meili , Song Hua , Davis Dionne , Gilbert Mark 
Published: November 2022

Abstract

INTRODUCTION
Immune therapeutic strategies are ideal for exploiting glial tumor heterogeneity. A limitation to their implementation for intra-axial brain tumors has been corticosteroids. Steroid use is associated with worse progression-free and overall survival when combined with some immunotherapies. Dexamethasone remains first line treatment for vasogenic cerebral edema and a primary therapy for immune-related adverse events secondary to immunotherapies. While used for decades, steroid immunosuppressive effects remain insufficiently characterized. We examined the temporal effects of dexamethasone on an extensive repertoire of immune cell subtypes.

METHODS
Non-tumor bearing C57BL/6 mice were treated with a onetime dose of 1 mg/kg dexamethasone via gavage, and peripheral blood was sampled at timepoints spanning 1 hour to 7 days. Flow cytometry was performed in triplicate to determine absolute cell counts of circulating B cells, CD8+ T cells (naive/memory), CD4+ T cells (naive/memory/regulatory), NK cells, neutrophils, monocytes, and eosinophils at each timepoint. We examined T cell function at multiple timepoints using an anti-CD3/CD28 bead stimulation assay.

RESULTS
At 1-hour post-treatment, cell counts across lymphoid subtypes increased. Neutrophils dramatically increased, while the remaining myeloid subtypes began to decrease. NK cells, similarly, were decreased in number. At 4-hours post-treatment all immune subtypes had their lowest circulating counts. There were corresponding increases in CD8+ and CD4+ T cell expansion and proliferation indices at 4-hours. By 24-hours post-treatment, all immune subtypes had recovered to or surpassed pre-treatment counts, except monocytes. By 7 days, the Tregs increased to 186% of pre-treatment counts, the highest of all subtypes, while eosinophils, monocytes, and NK cells never fully recovered to their pre-treatment baselines.

CONCLUSIONS
Understanding dexamethasone influence on circulating immune cells will inform optimal treatment timing for immunotherapies in brain tumor patients. We are further characterizing transcriptomic changes within immune cell subtypes following dexamethasone administration via population-level RNA sequencing over time.
IMMU-42. ADOPTIVE HEMATOPOIETIC STEM CELL AND APD1 THERAPY CONVERGE IN THE THYMUS TO PROMOTE ANTI-GLIOBLASTOMA IMMUNITY
Authors: Francis Connor , Font Laura Falceto , Figg John , Dean Bayli DiVita , Sebastian Mathew , Jin Dan , Long-James Kaytora , Von Roemeling Christina , Reid Alexandra , Moore Ginger , Mitchell Duane , Flores Catherine 
Published: November 2022

Abstract
Our lab previously published that adoptive hematopoietic stem cell (HSC) therapy administered in conjunction with aPD1 increases median survival in multiple models of CNS malignancies. Tumor-infiltrating lymphocytes (TIL) abundance is independently associated with better outcomes in many cancers. Impressively, approximately 25% of TILs are HSC-derived in early disease. Importantly, we show HSC therapy generates de novo TILs in a thymus-dependent fashion and offer evidence of altered central tolerance following aPD1 therapy, which may permit immune activation against a larger pool of tumor-associated antigens. Therapeutic HSCs were prepared from constitutive GFP-expressing (CD45.2+) and PD1KO (CD45.2+) mice and transferred into CD45.1+ hosts. Sublethal 5Gy total body irradiation was administered day 5 post-intracranial tumor implantation. The next day, 1E6 HSCs from a 1:1 – GFP:PD1KO cocktail were injected intravenously. Descriptive statistics are reported as mean ± SD. Transferred HSCs engraft, expand, differentiate, and migrate to form approximately 25% of the TIL compartment in only 15 days. We found that, 56.2% ± 20.3 of CD3+ TILs display a thymocyte-like CD4+CD8+ (DP) phenotype in early disease, and 43.8% ± 17.4 of these DP-TILs are HSC-derived. Interestingly, DP-TILs were virtually absent in advanced disease 29 days after treatment. At this stage, HSC-derived TILs most commonly fell within the single-positive (SP) TIL subsets, comprising 9.8% ± 5.6 of SP-CD8+ TILs. Notably, HSCPD1KO-derived cells were 4x more abundant amongst SP-CD8 TILs when compared to HSCGFP-derived cells (6.5% vs 1.6%, p &lt; 0.05). SP-CD8 thymocytes were similarly enriched for HSCPD1KO progeny (41.1% vs 24.7%, p &lt; 0.05) which may suggest PD-1 blockade directly promotes thymopoiesis. The privileged maturation of PD1-deficient HSCs is intriguingly reversed when GFP:PD1KO HSCs are co-transferred into non-tumor-bearing mice. Thus, we show the thymus is an active site where PD-1-blocking agents function, and that HSC + aPD1 therapy is uniquely positioned to leverage thymus-dependent anti-tumor immunity.
INNV-08. CASE REPORT OF AN OLDER GLIOBLASTOMA PATIENT SURVIVING MORE THAN 12 YEARS AFTER TREATMENT WITH CILENGITIDE IN ADDITION TO STANDARD THERAPY
Authors: Alalami Huda , Hu Jethro , Fan Xuemo , Bannykh Serguei 
Published: November 2022

Abstract

BACKGROUND
Glioblastoma is the most common malignant brain tumor. Less than 1% of patients survive longer than 10 years. Integrins are implicated in tumorigenesis due to their role in cell adhesion and intercellular communication. Cilengitide, a selective αvβ3, and αvβ5 integrin inhibitor, was studied for patients with glioblastoma.

RESULTS
A 77-year-old woman was found to have a left temporoparietal MGMT methylated glioblastoma after presenting with visual field deficits in 2009. She underwent near gross total resection of the tumor. The tumor had retained expression of PTEN and MAPK. No mutations in IDH or ATRX were detected. Genetic testing revealed mutations in TERT promoter, TP53, SYNE1, NF1, PTEN, FBXW7, POLD1, ERG, and PRKDC. She was enrolled in the CENTRIC trial, a phase III clinical trial studying the addition of cilengitide to standard therapy for patients with newly diagnosed glioblastoma with methylated MGMT promoter. In 2013, the initial results of the study failed to meet the endpoint of prolonged overall survival and progression-free survival, therefore the study was halted. The patient received cilengitide through compassionate use until 2016. Surveillance brain MRI obtained every three shows no radiographic evidence of recurrence.

CONCLUSION
Although it is known that methylated-MGMT promoter is one of the few positive prognostic factors in GBM, overall survival remains poor in older patients. This case highlights a rare clinical response to treatment in an older female who has survived more than 12 years without disease recurrence after receiving cilengitide in addition to standard therapy. Her outcome may have been influenced by the expression of PTEN and the methylation of MGMT, which are associated with improved outcomes. Although the development of cilengitide was halted for lack of efficacy, the existence of individual responders such as this patient suggests that further study of integrin inhibition for glioblastoma patients may be worth pursuing.
INNV-11. EIGHTEEN YEARS OF EXPERIENCE WITH TREATMENT OF GLIOBLASTOMA USING TUMOR TREATING FIELDS (TTFIELDS) IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM) IN A SINGLE CENTER
Authors: Vymazal Josef , Novák Tomáš , Slanina Petr , Kazda Tomáš , Sroubek Jan , Klener Jan , Hrbáč Tomáš , Syrucek Martin , Rulseh Aaron 
Published: November 2022

Abstract
Despite considerable progress in the management of many malignant tumors, the prognosis of the most malignant primary brain tumor, GBM, remains unfavorable. TTFields utilize low intensity electric fields with intermediate frequency (100–500 kHz) that act as an antimitotic, selectively inhibiting growth of rapidly dividing tumor cells by disrupting multiple phases of the cell cycle (metaphase, anaphase, and telophase) resulting in cellular apoptosis. TTFields are delivered via arrays of transducers placed on the patients’ scalp. Between 2004 and August 2021, 54 patients (KPS ≥, 20 female), aged 21.85–77.77 years (mean age 47.41 ± 11.92 years; median 47.88 years) were treated with TTFields for ndGBM, and compared to 52 control patients (15 females); aged 27.03–76.67 years (mean age 51.38 ± 12.55 years; median 51.74 years. All patients from both groups underwent gross total or partial resection of GBM. When available, MGMT promoter methylation status was comparable in both groups. The most frequent AE from TTFields therapy was skin irritation at the array site that usually responded to local corticosteroid application. Patients on TTFields therapy demonstrated improvements in PFS and OS relative to controls (hazard ratio: 0.55, p=0.006; and 0.61, p=0.027 respectively). TTFields average time on therapy was 74.8% (median 82%): median PFS of these patients was 18.16 months. Seven patients with TTFields usage ≤ 60% (23–60%, mean 46.3%, median 53%) had a median PFS of 7.95 months (p=0.0356). Control patients with no TTFields exposure had a median PFS of 11.04 months. In conclusion, this is one of the most extensive studies of ndGBM patients treated with TTFields, covering a period of 18 years in a single center. We demonstrate positive effects of TTFields on both PFS and OS in patients with ndGBM.
INNV-13. INDOLENT H3 K27-ALTERED DIFFUSE MIDLINE GLIOMA
Authors: Damodharan Sudarshawn , Helgager Jeffrey , Puccetti Diane 
Published: November 2022

Abstract

INTRODUCTION
H3 K27-altered diffuse midline glioma (DMG) is an aggressive central nervous system tumor that is universally fatal with a median survival of 8-12 months after diagnosis. Here we present a patient who was incidentally found to have a lesion within the right thalamus on brain magnetic resonance imaging (MRI). Twelve years later, she was found to have a brain mass within the same area with pathology consistent with an H3 K27-altered DMG. Case Description: A 14-year-old female presented with new onset left sided numbness and weakness, blurry vision and a right sided temporal headache. Her past medical history is significant for severe persistent asthma and anoxic brain injury secondary to a cardiopulmonary arrest at 2-years-of-age due to an asthma exacerbation. She has had multiple MRIs of her brain since her initial insult which initially showed the presence of a T2/FLAIR hyperintense lesion within the right medial thalamus in addition to chronic central nervous system changes. The right thalamic lesion was stable in size between images obtained at 2-years and 4-years of age. Her current physical exam is significant for decreased strength to her left upper and lower extremities. Brain MRI with and without contrast is obtained, demonstrating partial effacement of the third ventricle due to mass effect from an enlarging mass from the right thalamus. Biopsy of the lesion demonstrated an H3 K27-altered DMG, WHO grade 4. Our patient went on to receive palliative radiation therapy with 59.4 Gy over 33 fractions.

DISCUSSION
This case illustrates an unusual presentation of an H3 K27-altered DMG with an indolent course, diagnosed twelve years after the initial MRI finding. This proposes the possibility of multiple factors playing a role in the oncogenesis of these aggressive tumors and that further research is warranted.
INNV-18. PROLONGED REMISSION AFTER TREATMENT WITH SINGLE-AGENT IBRUTINIB AS MAINTENANCE THERAPY FOLLOWING SALVAGE RADIATION THERAPY FOR REFRACTORY/RELAPSE PRIMARY CNS LYMPHOMA
Authors: Du Steven , Bota Daniela , Kong Xiao-Tang 
Published: November 2022

Abstract

INTRODUCTION
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease. Standard induction therapy for PCNSL consists of a high-dose methotrexate-based (HD-MTX) regimen. For relapsed or refractory primary CNS lymphoma (r/r PCNSL), most of the non-standard treatment regimens including additional chemotherapy, stem cell transplant, or whole brain radiation therapy (WBRT) may not reach long-term remission due to intolerance of the treatment by the patients or lack of effects. Here we report a case with r/r PCNSL reached more than 50-month remission after salvage WBRT followed by single agent ibrutinib maintenance therapy. CASE REPORT: a 75-year-old female with PCNSL, experienced disease recurrence, despite undergoing multiple lines of treatment including initial HD-MTX, second-line rituximab and temozolomide, repeated HD-MTX, and a clinical trial. Because her disease was refractory to these treatment options, we decided to start WBRT as salvage therapy, which resulted in significant reduction of tumor burden. Prior studies, however, showed that r/r PCNSL patients who underwent salvage WBRT alone had a median survival of only 1-2 years. Therefore, to extend the remission after salvage WBRT, she opted to try ibrutinib, a Bruton’s tyrosine kinase inhibitor with past success in treating r/r PCNSL patients, as maintenance therapy after salvage WBRT. She tolerated well and decided to be off the treatment after 18 month-maintenance therapy. The patient has been stable clinically. She has since survived for more than 50 months after the completion of salvage WBRT plus maintenance therapy with ibrutinib.

DISCUSSION
Compared to prior reports of 11 to 16 months of median survival after salvage WBRT alone for r/r PCNSL, our case has had prolonged survival, which supports the potential positive effect of ibrutinib as maintenance therapy for r/r PCNSL after salvage WBRT
INNV-19. THE DETECTION OF DISSEMINATED PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION (PPTID) IN CEREBROSPINAL FLUID (CSF) USING CELL CAPTURE AND IMMUNOCYTOCHEMISTRY
Authors: Armijo Kaitlyn , Sweed Nathan , Hsiao Steven , Pircher Tony , Marrin Mikayla , Cho Leslie , Kreitzburg Kelly , Blouw Barbara , Fisher Deanna , Dugan Michael , Kesari Santosh 
Published: November 2022

Abstract

BACKGROUND
Pineal parenchymal tumors of intermediate differentiation (PPTID) account for 21% to 54% of pineal parenchymal tumors and may be complicated by cerebrospinal dissemination (most commonly at time of reoccurrence; up to 4-10 years post resection). The integral membrane protein synaptophysin is expressed in neuroendocrine cells and virtually all neuraxial neurons that contribute to synaptic transmission. PPTID frequently demonstrates synaptophysin independently of other neural differentiation markers. Cerebrospinal fluid (CSF) cell capture assays have demonstrated utility for assessing disseminated intracranial neoplasms, thus we explore this technology for monitoring a patient with PPTID.

METHODS
A 30-year-old female patient with PPTID diagnosed two years prior was suspected for intracranial dissemination and underwent five CSF collections over the course of 64 days. Per collection, approximately 7 mL of CSF was submitted for each cytology and cell capture. Cytology was performed at Providence Saint John’s Health Center. The CNSide™ platform (Biocept, Inc.) was used to capture and stain cells for DAPI, synaptophysin, and CD45. Multiple capture antibody cocktails (termed 1986, 1822, and gTP1—originally developed for use in carcinoma, melanoma, and glioma) were tested. Cells of interest (COI) were defined by positive immunoreactivity for both DAPI and synaptophysin and no immunoreactivity for CD45. Results were quantified and compared longitudinally.

RESULTS
CSF analysis on days 0, 9, 21, 36, and 64 demonstrated negative results by cytology and 51, 96, 170, 130, and 43 COI/mL by the CNSide platform, respectively. Cumulative mean capture rates for cocktails 1986, 1822, and gTP1 were 47, 14, and 36 COI/mL/sample, respectively.

DISCUSSION
A significant amount of PPTID patients will develop cerebrospinal dissemination. The importance of craniospinal control in this setting has been previously demonstrated. Our work suggests that cell capture assays paired with immunocytochemistry can be used as sensitive means to monitor disseminated PPTID and may impact treatment decisions.
INNV-24. PATIENT SATISFACTION AND COST ANALYSIS OF THE TELEMEDICINE PROGRAM WITHIN A NEURO-ONCOLOGY PROGRAM
Authors: Bilenkin Arkady , Kang Richard , Prorok Rachel , Rogers Andrea , Naso Cristina , Patel Krupal , Beer-Furlan Andre , Liu James 
Published: November 2022

Abstract
Unique challenges exist in the utilization of telemedicine for neurological and surgical specialties. We examined the differences in patient satisfaction for telemedicine versus in-person Press Ganey survey reports within an integrated Neuro-Oncology Department to assess whether there was a difference between surgical and medical specialties. We also examined the potential cost savings benefits of utilizing telemedicine. 1189 Press Ganey surveys in the Department of Neuro-Oncology (982 in-person and 207 telemedicine) submitted by neurosurgical and neuro-oncology patients between 04/01/2020 and 06/30/2021 were analyzed. Survey results were divided into 4 categories (Access, Provider, Technology (for telemedicine only), and Overall Satisfaction). Results were compared between telemedicine and in-person visits, and by gender, age, insurance, and specialty. Potential time and cost savings were estimated by calculating lost productivity based on census income data with motor vehicle expenses, and round-trip distances with mean visit durations, respectively. The survey results demonstrated that, among telemedicine patients, there were no differences in satisfaction based on gender, age, or insurance. Surgical specialties scored higher in Access, Technology, and Overall. Among in-person patients, patients older than 65 had higher satisfaction for Provider (p=0.0368) and Overall (p=0.0010). Medicare patients returned higher scores compared to non-private insurance for Overall (p=0.0172). Surgical patients scored higher for Access (p=0.0002). When comparing Telemedicine to In-Person scores, In-person satisfaction was higher for Provider for all patients combined. For surgical patients only, Telemedicine scored higher only in Access (p=0.0252). Cost analysis demonstrated that patients saved an average of 155.4 to 175.1 miles and 3.1 to 3.4 hours of travel per visit and average cost savings were $117.84 to $185.00. We conclude that telemedicine lessens the financial and time burden on neuro-oncology patients and yields non-inferior patient-satisfaction when employed in neurosurgery as compared to medicine, despite potential limitations of the technology in neurological and surgical specialties.