tbuckley/cabot-search huggingface dataset:
Abstract P342: Development of a Mixture Model With Smoothing Functions of Trajectories
Authors: Ming Ding, Garrett Fitzmaurice
Journal: Circulation (2020)

In the health and social sciences, two types of mixture model have been widely used by researchers to identify heterogeneous trajectories of participants within a population: latent class growth analysis (LCGA) and the growth mixture model (GMM). Both methods parametrically model trajectories of individuals, and capture latent trajectory classes, by using an expectation-maximization (E-M) algorithm. However, parametric modeling of trajectories using polynomial functions or monotonic spline functions results in limited flexibility for modelling trajectories; as a result, group membership may not be classified accurately due to model misspecification. In this paper, we propose a mixture model (SMM) allowing for smoothing functions of trajectories using a modified E-M algorithm. In the E step, participants are reassigned to only one group for which the estimated trajectory is the most similar to the observed one; in the M step, trajectories are fitted using generalized additive mixed models (GAMM) models with smoothing functions of time. This modified E-M algorithm is straightforward to implement using the recently released “gamm4” macro in R. The SMM can incorporate time-varying covariates and be applied to longitudinal data with normal, Bernoulli, and Poisson distributions. Simulation results show favorable performance of the SMM in terms of classification of group membership. The proposed method is illustrated by its application to body mass index data of individuals followed from adolescence to young adulthood and the relationship with incidence of cardiometabolic disease.
NCMP-25. CLINICAL FEATURES, NEUROLOGIC RECOVERY, AND RISK PREDICTION OF POST-OPERATIVE POSTERIOR FOSSA SYNDROME: A PROSPECTIVE STUDY
Authors: Raja B Khan, Zoltan Patay, Paul Kilmo, Jie Huang, Arzu Onar-Thomas, Rahul Kumar, Frederick A Boop, Darcy Raches, Heather Conklin, Richa Sharma, Andrea Simmons, Zsila Sadighi, Amar Gajjar
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery. METHODS Children with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT 01878617). RESULTS Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p&amp;lt; 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p&amp;lt; 0.0001) were association with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery. CONCLUSION Categorizing PFS in to types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 remained non-ambulatory at 12-month follow-up. Surgical experience was a major modifiable contributor to the development of PFS.
INNV-23. LIFESTYLE COACHING IS FEASIBLE AND IMPROVES PILOT OUTCOMES IN FATIGUED BRAIN TUMOUR PATIENTS: THE BT-LIFE (BRAIN TUMOURS, LIFESTYLE INTERVENTIONS, AND FATIGUE EVALUATION) MULTI-CENTRE, PHASE II RCT
Authors: Alasdair G Rooney, William Hewins, Amie Walker, Lisa Withington, Mairi Mackinnon, Sara Robson, Aimee Green, Garry Anderson, Helen Bulbeck, Carol Cochrane, David Gillespie, Christopher Hewitt, Julia Day, Claire Torrens, Julie Emerson, Jo Dunlop, Michelle Welsh, Lisa Hopcroft, Mary Wells, Catherine McBain, Anthony Chalmers, Robin Grant
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Fatigue is common and disabling for brain tumour patients. We studied the feasibility of two innovative lifestyle coaching interventions for high fatigue. METHODS Multi-centre phase II feasibility RCT (ISRCTN17883425). Adult primary brain tumour outpatients reporting significant fatigue (Brief Fatigue Inventory [BFI] score 4+), were randomised to one of three arms: Control; Health Coaching (“HC”, comprising eight structured coaching sessions on lifestyle behaviours); or HC plus Activation Coaching (“HC+AC”, adding two structured interviews targeting motivation to change). Outcomes were measured at baseline (T0), after interventions (T1), and at 16 weeks (T2). The primary outcome of feasibility was required for both recruitment (aim: average n= 5 fatigued patients recruited/month) and retention (aim: minimum 60% retention at T2). Secondary pilot outcomes included change in fatigue, depressive symptom, and QOL measures. RESULTS Over a nine-month recruitment period, n= 46 fatigued brain tumour patients were recruited (average n=5.1/month) and n= 34 were retained to endpoint (retention at T2= 73%), meeting the primary outcome of feasibility. Surprisingly, fatigue reduced significantly after HC (T1 mean change in BFI score from T0 baseline, relative to the equivalent change in control group: HC= -2.3 points [95%CI -3.4/-0.3]; HC+AC= -2.0 [-2.9/+0.1]; ANOVA p= 0.02) and was reduced in magnitude in both intervention groups at T2 (p= N.S). Both interventions also improved depressive symptoms (T1 mean change in HADS-Depression: HC= -2.0 points [-5.6/-0.1]; HC+AC= -2.9 [-6.5/-1.0]; Kruskal-Wallis p= 0.02). Patient-nominated QOL outcomes improved persistently after HC+AC (T2 mean change in PSYCHLOPS score: HC= -2.4 points [-5.4/+2.8]; HC+AC= -6.1 [-9.2/-0.8]; ANOVA p= 0.01). CONCLUSION Innovative coaching interventions, focused on lifestyle factors, are feasible to deliver to fatigued brain tumour patients. Preliminary signals suggest that these non-drug approaches may benefit several mediators of quality of life and warrant further study.
GCT-38. RELAPSE PATTERNS OF INTRACRANIAL GERMINOMAS BEFORE AND AFTER ENDOSCOPIC ERA
Authors: Takao Tsurubuchi, Shingo Takano, Ai Muroi, Kei Hara, Masahide Matsuda, Hiroyoshi Akutsu, Masashi Mizumoto, Hiroko Fukushima, Ryoko Suzuki, Yuni Yamaki, Eiichi Ishikawa, Akira Matsumura
Journal: Neuro-Oncology (2020)

Abstract PURPOSE We evaluated the relapse patterns of CNS germinomas before and after introducing neuroendoscopic biopsy in 2000. METHODS We retrospectively assessed the relapse patterns of 57 patients treated as pure germinoma or germinoma with STGC between 1980 and 2019 at University of Tsukuba, partially containing the patients of the previous report (Takano S et al., World Neurosurg, 2015). Median age was 15 y.o.(7y.o.~38y.o.), and men was 80.7%. Tumor locations were pineal 35, sellar 19, basal ganglia 3, others 11. Group A;1980~1999 was 20, and group B;2000~2019 was 37. From 1980 to 1994, whole brain irradiation(WB) 30.6 Gy plus whole ventricle irradiation(WV) 19.8 Gy. From 1995 to 1999, WV 26~30.6 Gy with Chemotherapy(Chem) or Chem alone. Since 2000, Chem for 3 kurr with WV 24~30.6 Gy, and 6–19.8 Gy as local boost to residual lesion. RESULTS Follow up periods were median 121 M(4.5M~386M; group A), and median 89 M(4 M~231 M; group B). Six patients(30%) recurred in the group A, as ex field 4(1;brain and extramedullary, 1;brain and paranasal sinus, 1;LV &amp; third ventricle, 1;extramedullary), in field 1(LV). Chem only 1(LV &amp; third ventricle). Two patients(5.4%) recurred in the group B, as ex field 2(1;intramedullary, 1;extramedullary). The group A showed CR;18, PR;1, Dead;1(Dissemination), and the group B showed CR;35, PR;1 Dead;1(Encephalopathy). CONCLUSION WV and Chem prevented extrafield recurrence keeping good quality of life. Neuroendscopy biopsy with ETV did not increase CSF seeding.
LGG-47. SYSTEMIC THERAPY OF ROSETTE-FORMING GLIONEURONAL TUMOR OF THE FOURTH VENTRICLE INAN ADOLESCENT
Authors: Rene McNall-Knapp, Naina Gross, Wafik Zaky, Benjamin Cornwell, Theresa Gavula, Abhishek Bavle
Journal: Neuro-Oncology (2020)

Abstract An 11 y.o. female presented to a GI specialist with complaints of morning vomiting and periumbilical abdominal pain for several months. Had progressing symptoms with GI work-up for ~1 year. She developed diplopia and worsening headaches. Imaging revealed a T2/FLAIR hyperintense mass in the 4th ventricle with heterogeneous enhancement and obstructive hydrocephalus. Three T2 bright, non-enhancing, subcentimeter masses identified in the right cerebellum. Due to poor differentiation between tumor and normal tissue at brainstem, only partial resection (PR) was feasible. Pathology initially called pilocytic astrocytoma (PA). All symptoms resolved after PR. Slow progression in the tumor and “satellite” lesions noted over two years. Second opinion and molecular typing reclassified the tumor as rosette-forming glioneuronal tumor (RFGNT) with a mutation in PIK3CA. Therapy started with vinblastine and carboplatin with stable disease x 7 months, discontinued due to allergic reaction to carboplatin. Initiated therapy with everolimus, an mTOR inhibitor. The tumor’s characteristics on imaging changed with initial growth and increase in peripheral enhancement in one satellite and the primary tumor. Nevertheless, we persevered. When comparing pre-treatment MRI to most recent 7 months later, there has been an overall decrease in volume of expansile heterogenous tumor along the margins of the fourth ventricle. The degree of peripheral enhancement associated with the mass has increased. RFGNT is a rare tumor included in WHO classification since 2007. Ellezam et al identified recurrent PIK3CA mutations. To our knowledge, this is the only report of treatment targeting the mutation. We report a radiographic response despite initial growth.
Tofacitinib restores the balance of γδTreg/γδT17 cells in rheumatoid arthritis by inhibiting the NLRP3 inflammasome
Authors: Xinyu Yang, Ning Zhan, Yang Jin, Hanzhi Ling, Chipeng Xiao, Zhen Xie, Hao Zhong, Xinxin Yu, Runhua Tang, Jinglan Ma, Jubo Guan, Guoyu Yin, Gan Wu, Liangjing Lu, Jianguang Wang
Journal: Theranostics (2020)

Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, γδTreg/γδT17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp3-/- mice were introduced to assess the influence of NLRP3 on γδT17 cell activation in RA. Results: TOF treatment decreased levels of γδT17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the γδTreg/γδT17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1β via downregulation of NLRP3. Furthermore, experiments using Nlrp3-/- mice verified that the NLRP3 inflammasome mediated the effect of TOF on γδT17 cell activation. Conclusions: Recovery of γδTreg/γδT17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated γδT17 cell activation.
GCNG: graph convolutional networks for inferring gene interaction from spatial transcriptomics data
Authors: Ye Yuan, Ziv Bar-Joseph
Journal: Genome biology (2020)

Abstract Most methods for inferring gene-gene interactions from expression data focus on intracellular interactions. The availability of high-throughput spatial expression data opens the door to methods that can infer such interactions both within and between cells. To achieve this, we developed Graph Convolutional Neural networks for Genes (GCNG). GCNG encodes the spatial information as a graph and combines it with expression data using supervised training. GCNG improves upon prior methods used to analyze spatial transcriptomics data and can propose novel pairs of extracellular interacting genes. The output of GCNG can also be used for downstream analysis including functional gene assignment. Supporting website with software and data: https://github.com/xiaoyeye/GCNG .
EXTH-73. HETEROGENEITY IN CELL SURFACE ANTIGEN AND HLA CLASS I EXPRESSION IN PEDIATRIC BRAIN TUMORS AND ITS IMPACT ON T-CELL IMMUNOTHERAPY
Authors: Haley Houke, Xiaoyan Zhu, Kimberly S Mercer, Jennifer L Stripay, Jason Chiang, Suzanne Baker, Martine F Roussel, Stephen Gottschalk, Giedre Krenciute
Journal: Neuro-Oncology (2020)

Abstract Immunotherapy with tumor antigen-specific chimeric antigen receptor (CAR) and/or ab (T-cell receptor) TCR T-cells has the potential to improve clinical outcomes of patients with pediatric brain tumors. As a prerequisite for successful T-cell therapies, we must determine which cell surface antigens are expressed and targetable in these tumors, and if HLA Class I is present, which is necessary for ab TCR T-cell recognition. Therefore, in this study we systematically analyzed pediatric patient-derived orthotopic xenograft (PDOX) brain tumor samples for cell surface expression of five known CAR targets: IL13Ra2, HER2, EphA2, B7-H3, and GD2, as well as HLA Class I. We established and validated a flow cytometry-based method of profiling tumor-associated antigens. Fifty-three PDOX samples have been profiled to date, including medulloblastoma, high grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), atypical teratoid rhabdoid tumor (ATRT), and ependymoma, among others. Our results showed high variability within and between individual samples. B7-H3 was the most consistently expressed, seen in 98% of the samples tested. We validated these results by conventional immunohistochemistry staining for B7-H3 and found comparable RESULTS: HLA Class I was highly expressed on all HGG samples but was undetectable on 47.8% of other brain tumor samples. This suggests that down-regulation of HLA class I is one mechanism by which brain tumors evade conventional T-cells, and that HLA-independent CAR T-cells would be useful therapies. We also compared expression of antigens in fresh patient samples and corresponding PDOX tumors and saw that they were indeed similar. To our knowledge, this is the largest group of pediatric brain tumor PDOX samples methodically analyzed for potential CAR target antigens and HLA Class I. Taken together, our data demonstrate that elimination of tumors by CAR T-cell immunotherapies will require targeting multiple antigens, and our profiling method could inform how to circumvent antigen-negative relapse.
<scp><i>CDKN2A</i></scp> deletions are associated with poor outcomes in 101 adults with T‐cell acute lymphoblastic leukemia
Authors: Huan‐Ping Wang, Yi‐Le Zhou, Xin Huang, Yi Zhang, Jie‐Jing Qian, Jian‐Hu Li, Xue‐Ying Li, Chen‐Ying Li, Yin‐Jun Lou, Wen‐Yuan Mai, Hai‐Tao Meng, Wen‐Juan Yu, Hong‐Yan Tong, Jie Jin, Hong‐Hu Zhu
Journal: American Journal of Hematology (2020)

The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.
EXTH-61. COMBINATION OF DISULFIRAM AND COPPER INDUCES NPL4 AGGREGATION, TARGETS CD133-NESTIN CELLS AND EXTENDS SURVIVAL IN MEDULLOBLASTOMA GROUP 3 MODELS
Authors: Riccardo Serra, Tianna Zhao, Sakibul Huq, Noah Gorelick, Joshua Casaos, Arba Cecia, Antonella Mangraviti, Alessandro Olivi, Henry Brem, Eric M Jackson, Betty Tyler
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Medulloblastoma (MB), the most common brain malignancy among children, is classified into four molecular subtypes, WNT-driven, Shh-driven, Group 3 and 4. The aim of this study was to assess the effects of the combination of Disulfiram, an inhibitor of Aldehyde Dehydrogenase, and Copper in Shh-driven and Group 3 MB, in vitro and in vivo. METHODS The mechanisms of action and anti-cancer stem-cell effects of disulfiram were evaluated with clonogenic assays, flow-cytometry (FC), western blotting (WB), and immunofluorescence (IF) using established MB cell-lines - ONS76, UW228, D425med, D341 and D283- representing the main molecular subtypes. Survival, tumor volume, nuclear protein localization protein-4-expression (NPL4) and markers of proliferation/apoptosis were assessed in multiple models of Group 3 MB in vivo and ex vivo with WB and immunohistochemistry (IHC). RESULTS Significant in vitro cytotoxicity was demonstrated at nanomolar concentrations of DSF in all lines. DSF/Cu++ induced cell death (increased AnnV/PI, cleaved-Poly(ADP-ribose)polymerase fraction, and Apoptosis Inducing Factor on WB/FC/IF, in vitro and ex vivo) through NPL4 accumulation in cell nucleus and intracellular buildup of poly-ubiquitylated proteins. DNA damage was also detected with WB and H2AX foci on immunofluorescence. Flow-cytometry analysis demonstrated a significant reduction in ALDH, Nestin- and CD133-positive cells in Group 3 lines, confirmed with WB in vitro and ex vivo. DSF/Cu++-toxicity was tested in vivo in multiple dose-escalating trials, and the combination significantly prolonged survival and reduced tumor volume in D425 and D341 xenografts. IHC showed lower Ki67 and increased Cleaved-Caspase-3 expression, higher NPL4-positive cells and no difference in NeuN and GFAP-positive cells after treatment. CONCLUSIONS DSF/Cu++ demonstrated a potent therapeutic effect on Shh-driven and Group 3 MB cell lines by determining apoptosis, targeting cancer stem cells and inducing DNA damage. Our data suggest that this combination may serve as a novel treatment, alone or with existing therapies, for pediatric MB.
Insights into the genetic architecture of the human face
Authors: Julie D. White, Karlijne Indencleef, Sahin Naqvi, Ryan J. Eller, Hanne Hoskens, Jasmien Roosenboom, Myoung Keun Lee, Jiarui Li, Jaaved Mohammed, Stephen Richmond, Ellen E. Quillen, Heather L. Norton, Eleanor Feingold, Tomek Swigut, Mary L. Marazita, Hilde Peeters, Greet Hens, John R. Shaffer, Joanna Wysocka, Susan Walsh, Seth M. Weinberg, Mark D. Shriver, Peter Claes
Journal: Nature Genetics (2020)
DIPG-59. UPREGULATION OF PRENATAL PONTINE ID1 SIGNALING IN DIPG
Authors: Micah K Harris, Viveka Nand Yadav, Stefanie Stallard, Rinette Woo, Robert Siddaway, Tingting Qin, Brendan Mullan, Zachary Miklja, Ruby Siada, Ramya Ravindran, Xuhong Cao, Amy Pasternak, Maria G Castro, Pedro R Lowenstein, Rajen Mody, Arul Chinnaiyan, Cynthia Hawkins, Pierre Desprez, Sean McAllister, Sriram Venneti, Carl Koschmann
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Diffuse intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors with no curative therapies. Inhibitor of DNA binding (ID) proteins are key regulators of gene differentiation during embryogenesis. Previous work has shown that H3F3A and ACVR1 mutations increase ID1 expression in cultured astrocytes, but this has not been validated in human DIPG, nor has the regulation and targetability of ID1 been explored in DIPG. RESULTS Analysis of post-mortem tissue and multiple human datasets showed ID1 to be elevated in DIPG, and to correlate with reduced survival. In a multi-focal autopsy of a DIPG case, we also found ID1 expression to be heterogeneous and to correlate with tumor invasion. Chromatin immunoprecipitation qPCR (ChIP-qPCR) revealed elevated H3K27ac and low H3K27me3 at ID1 regulatory regions (enhancers/promoters) in DIPG tissue compared to normal brain, regardless of H3 or ACVR1 mutation status. Analysis of publicly-available ISH and ChIP-sequencing data of developing murine brains revealed H3K27ac at ID1 enhancers to be elevated in the prenatal hindbrain compared to prenatal forebrain and midbrain, and all postnatal brain regions. ID1 shRNA-mediated knockdown of primary human H3K27M DIPG cells (DIPG007) significantly reduced invasion and migration. We also treated DIPG007 cells with cannabidiol (CBD) and found reduced viability at clinically relevant dosing (IC50=2.4 uM) with dose-dependent reduction in ID1 protein. CONCLUSIONS These findings indicate that a multifactorial (genetic and regionally-based) epigenetic upregulation of ID1 drives DIPG invasiveness and is targetable with CBD. ID1 knockdown and CBD treatment experiments in murine models of DIPG are ongoing.
GCT-51. IMMUNE CHECKPOINT MOLECULES AND TUMOR INFILTRATING LEUKOCYTES IN THE TUMOR MICROENVIRONMENT ARE ASSOCIATED WITH THE GROWTH OF INTRACRANIAL GERMINOMAS
Authors: Masaaki Nishimoto, Kentaro Ohara, Dai Kamamoto, Ryota Tamura, Tomoru Miwa, Kazunari Yoshida, Hikaru Sasaki
Journal: Neuro-Oncology (2020)

Abstract The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear. In the present study, we investigated the expression of immune checkpoint molecules, as well as the number of tumor-infiltrating lymphocytes (TILs), in intracranial germinomas to determine whether there were any correlations between the statuses of these immune-related molecules/cells and clinical manifestations in patients with germinoma. The 8 patients were categorized based on the duration between symptom onset and pathological diagnosis into the long-term onset (LTO) group (&amp;gt; 1 year of symptoms, 3 patients) and the short-term onset (STO) group (&amp;lt; 1 year of symptoms, 5 patients). Compared with STO tumors, LTO tumors were significantly associated with a lower ratio of programed cell death ligand-1 (PD-L1)–positive tumor cells (p = 0.012), higher number of infiltrating CD3- and CD8-positive lymphocytes (p = 0.016, 0.003, respectively), and lower ratio of programed cell death-1 (PD-1)–positive cells per CD8–positive lymphocytes (p = 0.047). LTO germinomas were significantly smaller in size than STO tumors and tended to be present in patients with atypical tumor location. Our data suggest that the tumor immune microenvironment, including PD-1/PD-L1 signaling, is associated with the growth of intracranial germinomas. Immune checkpoint inhibitors might be a reasonable treatment option for recurrent germinomas or as replacement for radiotherapy in patients with intracranial germinomas.