Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma.

Abstract:

Background:Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint pathway in ACP and PCP. Methods:We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. Results:All ACP (15 ± 14% of cells, n = 23, average ± SD) and PCP (35 ± 22% of cells, n = 18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst lining. In PCP, PD-L1 was highly expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T cells. Conclusions:ACP exhibit PD-L1 expression in the tumor cyst lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Coy S,Rashid R,Lin JR,Du Z,Donson AM,Hankinson TC,Foreman NK,Manley PE,Kieran MW,Reardon DA,Sorger PK,Santagata S

doi

10.1093/neuonc/noy035

subject

Has Abstract

pub_date

2018-07-05 00:00:00

pages

1101-1112

issue

8

eissn

1522-8517

issn

1523-5866

pii

4917565

journal_volume

20

pub_type

杂志文章
  • Oxidative response gene polymorphisms and risk of adult brain tumors.

    abstract::Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hisp...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1215/15228517-2008-037

    authors: Rajaraman P,Hutchinson A,Rothman N,Black PM,Fine HA,Loeffler JS,Selker RG,Shapiro WR,Linet MS,Inskip PD

    更新日期:2008-10-01 00:00:00

  • Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma.

    abstract:Background:Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox117

    authors: Diamond EL,Prigerson HG,Correa DC,Reiner A,Panageas K,Kryza-Lacombe M,Buthorn J,Neil EC,Miller AM,DeAngelis LM,Applebaum AJ

    更新日期:2017-10-19 00:00:00

  • Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium.

    abstract:BACKGROUND:Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). MET...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov256

    authors: Poussaint TY,Vajapeyam S,Ricci KI,Panigrahy A,Kocak M,Kun LE,Boyett JM,Pollack IF,Fouladi M

    更新日期:2016-05-01 00:00:00

  • A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models.

    abstract::Difficulties of drug delivery across the blood-brain barrier (BBB) and failure to eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV-001) is a naturally occurring oncolytic picornavirus that can be systemically...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq148

    authors: Yu L,Baxter PA,Zhao X,Liu Z,Wadhwa L,Zhang Y,Su JM,Tan X,Yang J,Adesina A,Perlaky L,Hurwitz M,Idamakanti N,Police SR,Hallenbeck PL,Blaney SM,Chintagumpala M,Hurwitz RL,Li XN

    更新日期:2011-01-01 00:00:00

  • Assessment and treatment relevance in elderly glioblastoma patients.

    abstract::Glioblastoma (GBM) is the most common malignant primary brain tumor. Its incidence continues to increase in the elderly because the older segment of the population is growing faster than any other age group. Most clinical studies exclude elderly patients, and "standards of care" do not exist for GBM patients aged >70 ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou063

    authors: Bauchet L,Zouaoui S,Darlix A,Menjot de Champfleur N,Ferreira E,Fabbro M,Kerr C,Taillandier L

    更新日期:2014-11-01 00:00:00

  • Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells.

    abstract:INTRODUCTION:Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nos285

    authors: Alimova I,Birks DK,Harris PS,Knipstein JA,Venkataraman S,Marquez VE,Foreman NK,Vibhakar R

    更新日期:2013-02-01 00:00:00

  • Variation over time and interdependence between disease progression and death among patients with glioblastoma on RTOG 0525.

    abstract:BACKGROUND:We assessed the longitudinal hazard characteristics for death and progression in patients with glioblastoma, evaluated the impact of prognostic factors and treatment on the hazard within different time intervals to determine if effects are time varying, and quantified the influence of progression on survival...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/neuonc/nov009

    authors: Wang M,Dignam JJ,Won M,Curran W,Mehta M,Gilbert MR

    更新日期:2015-07-01 00:00:00

  • Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma.

    abstract:INTRODUCTION:Surgery is first-line therapy for glioblastoma, and there is evidence that gross total resection is associated with improved survival. Gross total resection, however, is not always possible, and relationships among extent (percent) of resection (EOR), residual volume (RV), and survival are unknown. The goa...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not137

    authors: Chaichana KL,Jusue-Torres I,Navarro-Ramirez R,Raza SM,Pascual-Gallego M,Ibrahim A,Hernandez-Hermann M,Gomez L,Ye X,Weingart JD,Olivi A,Blakeley J,Gallia GL,Lim M,Brem H,Quinones-Hinojosa A

    更新日期:2014-01-01 00:00:00

  • Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo.

    abstract::Multiphoton excitation fluorescent microscopy is a laser-based technology that allows subcellular resolution of native tissues in situ. We have recently applied this technology to the structural and photochemical imaging of cultured glioma cells and experimental gliomas ex vivo. We demonstrated that high microanatomic...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2006-034

    authors: Kantelhardt SR,Leppert J,Krajewski J,Petkus N,Reusche E,Tronnier VM,Hüttmann G,Giese A

    更新日期:2007-04-01 00:00:00

  • Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors.

    abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou083

    authors: Panageas KS,Reiner AS,Iwamoto FM,Cloughesy TF,Aldape KD,Rivera AL,Eichler AF,Louis DN,Paleologos NA,Fisher BJ,Ashby LS,Cairncross JG,Urgoiti GB,Wen PY,Ligon KL,Schiff D,Robins HI,Rocque BG,Chamberlain MC,Mason WP,

    更新日期:2014-11-01 00:00:00

  • REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy.

    abstract::The REV3L gene, encoding the catalytic subunit of human polymerase zeta, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of certain tumors. However, the role of REV3L in regulating the sensitivity of glioma cells to chemotherapy remains unknown. In this study, we investigated the expres...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2009-015

    authors: Wang H,Zhang SY,Wang S,Lu J,Wu W,Weng L,Chen D,Zhang Y,Lu Z,Yang J,Chen Y,Zhang X,Chen X,Xi C,Lu D,Zhao S

    更新日期:2009-12-01 00:00:00

  • Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies.

    abstract:BACKGROUND:Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS:Patients with CNS ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now132

    authors: Garber ST,Hashimoto Y,Weathers SP,Xiu J,Gatalica Z,Verhaak RG,Zhou S,Fuller GN,Khasraw M,de Groot J,Reddy SK,Spetzler D,Heimberger AB

    更新日期:2016-10-01 00:00:00

  • Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas.

    abstract::The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor117

    authors: Iwamoto FM,Hottinger AF,Karimi S,Riedel E,Dantis J,Jahdi M,Panageas KS,Lassman AB,Abrey LE,Fleisher M,DeAngelis LM,Holland EC,Hormigo A

    更新日期:2011-11-01 00:00:00

  • Prospective study of cigarette smoking and adult glioma: dosage, duration, and latency.

    abstract::Tobacco products are major contributors of exogenous N-nitroso compounds, a group of potent neurocarcinogens. Overall results from studies of smoking and brain tumors have been null, but have provided little information on duration, age at smoking initiation, and latency. We prospectively examined the relation between...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-005

    authors: Holick CN,Giovannucci EL,Rosner B,Stampfer MJ,Michaud DS

    更新日期:2007-07-01 00:00:00

  • Challenges to targeting epidermal growth factor receptor in glioblastoma: escape mechanisms and combinatorial treatment strategies.

    abstract::Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has th...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou222

    authors: Roth P,Weller M

    更新日期:2014-10-01 00:00:00

  • ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.

    abstract::Glioma is the most common adult primary brain tumor. Its most malignant form, glioblastoma multiforme (GBM), is almost invariably fatal, due in part to the intrinsic resistance of GBM to radiation- and chemotherapy-induced apoptosis. We analyzed B-cell leukemia-2 (Bcl-2) anti-apoptotic proteins in GBM and found myeloi...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor119

    authors: Day BW,Stringer BW,Spanevello MD,Charmsaz S,Jamieson PR,Ensbey KS,Carter JC,Cox JM,Ellis VJ,Brown CL,Walker DG,Inglis PL,Allan S,Reynolds BA,Lickliter JD,Boyd AW

    更新日期:2011-11-01 00:00:00

  • Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression.

    abstract::Current treatments for brain cancer have, for the most part, equivocal survival benefit. However, clinical trials of new anticancer agents do not adequately assess potential clinical benefits for patient function other than survival and time to tumor progression. We evaluated 56 patients with recurrent brain tumors wh...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/5.2.89

    authors: Meyers CA,Hess KR

    更新日期:2003-04-01 00:00:00

  • Enhanced expression of coproporphyrinogen oxidase in malignant brain tumors: CPOX expression and 5-ALA-induced fluorescence.

    abstract::In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluoresc...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,收录出版

    doi:10.1093/neuonc/nor116

    authors: Takahashi K,Ikeda N,Nonoguchi N,Kajimoto Y,Miyatake S,Hagiya Y,Ogura S,Nakagawa H,Ishikawa T,Kuroiwa T

    更新日期:2011-11-01 00:00:00

  • A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics.

    abstract::The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classifi...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/now277

    authors: van den Bent MJ,Weller M,Wen PY,Kros JM,Aldape K,Chang S

    更新日期:2017-05-01 00:00:00

  • Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    abstract:BACKGROUND:We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lu...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now037

    authors: Lee HJ,Hanibuchi M,Kim SJ,Yu H,Kim MS,He J,Langley RR,Lehembre F,Regenass U,Fidler IJ

    更新日期:2016-04-01 00:00:00

  • Copy number profiling across glioblastoma populations has implications for clinical trial design.

    abstract:Background:Copy number alterations form prognostic molecular subtypes of glioblastoma with clear differences in median overall survival. In this study, we leverage molecular data from several glioblastoma cohorts to define the distribution of copy number subtypes across random cohorts as well as cohorts with selection ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noy108

    authors: Cimino PJ,McFerrin L,Wirsching HG,Arora S,Bolouri H,Rabadan R,Weller M,Holland EC

    更新日期:2018-09-03 00:00:00

  • Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study.

    abstract::We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing o...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor173

    authors: Balducci M,Chiesa S,Diletto B,D'Agostino GR,Mangiola A,Manfrida S,Mantini G,Albanese A,Fiorentino A,Frascino V,De Bari B,Micciche' F,De Rose F,Morganti AG,Anile C,Valentini V

    更新日期:2012-01-01 00:00:00

  • Gadd45a sensitizes medulloblastoma cells to irradiation and suppresses MMP-9-mediated EMT.

    abstract::Medulloblastomas are the most common malignant tumors of the central nervous system during childhood. Radiation-induced medulloblastoma tumor recurrences are aggressive and metastatic in nature. In the present study, we demonstrate that Gadd45a expression can sensitize medulloblastoma cells to radiotherapy. We have el...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor109

    authors: Asuthkar S,Nalla AK,Gondi CS,Dinh DH,Gujrati M,Mohanam S,Rao JS

    更新日期:2011-10-01 00:00:00

  • Survivin transcript variant 2 drives angiogenesis and malignant progression in proneural gliomas.

    abstract:BACKGROUND:The influence of survivin isoforms on outcome in glioblastoma is poorly understood. We analyzed the dominant anti-apoptotic transcript variants of survivin using expression data and modeled them in vivo to determine their impact on glioma formation and progression. METHODS:Using data from low- and high-grad...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou034

    authors: Doucette T,Latha K,Yang Y,Fuller GN,Rao A,Rao G

    更新日期:2014-09-01 00:00:00

  • DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.

    abstract::We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and II...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq190

    authors: Zheng S,Houseman EA,Morrison Z,Wrensch MR,Patoka JS,Ramos C,Haas-Kogan DA,McBride S,Marsit CJ,Christensen BC,Nelson HH,Stokoe D,Wiemels JL,Chang SM,Prados MD,Tihan T,Vandenberg SR,Kelsey KT,Berger MS,Wiencke JK

    更新日期:2011-03-01 00:00:00

  • Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study.

    abstract::This study was conducted to determine the maximum tolerated dose and dose-limiting toxicity of irinotecan (CPT-11) administered every 3 weeks to adults with progressive malignant glioma who were treated with enzyme inducing antiepileptic drug (EIAED) therapy, and to compare the pharmacokinetics with those in patients ...

    journal_title:Neuro-oncology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1215/S1152851703000292

    authors: Prados MD,Yung WK,Jaeckle KA,Robins HI,Mehta MP,Fine HA,Wen PY,Cloughesy TF,Chang SM,Nicholas MK,Schiff D,Greenberg HS,Junck L,Fink KL,Hess KR,Kuhn J,North American Brain Tumor Consortium study.

    更新日期:2004-01-01 00:00:00

  • Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness.

    abstract:BACKGROUND:Malignant glioma is an aggressive cancer requiring new therapeutic targets. MicroRNAs (miRNAs) regulate gene expression post transcriptionally and are implicated in cancer development and progression. Deregulated expressions of several miRNAs, specifically hsa-miR-184, correlate with glioma development. MET...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou220

    authors: Emdad L,Janjic A,Alzubi MA,Hu B,Santhekadur PK,Menezes ME,Shen XN,Das SK,Sarkar D,Fisher PB

    更新日期:2015-03-01 00:00:00

  • Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway.

    abstract::Neuroblastomas, an embryonic cancer of the sympathetic nervous system, often occur in young children. Honokiol, a small-molecule polyphenol, has multiple therapeutic effects and pharmacological activities. This study was designed to evaluate whether honokiol could pass through the blood-brain barrier (BBB) and induce ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor217

    authors: Lin JW,Chen JT,Hong CY,Lin YL,Wang KT,Yao CJ,Lai GM,Chen RM

    更新日期:2012-03-01 00:00:00

  • Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma.

    abstract::Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nop035

    authors: Schwartzbaum JA,Huang K,Lawler S,Ding B,Yu J,Chiocca EA

    更新日期:2010-04-01 00:00:00

  • Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma.

    abstract:Background:Sonidegib (LDE225) is a potent, selective hedgehog (Hh) inhibitor of Smoothened. This study explored the safety and pharmacokinetics of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox109

    authors: Kieran MW,Chisholm J,Casanova M,Brandes AA,Aerts I,Bouffet E,Bailey S,Leary S,MacDonald TJ,Mechinaud F,Cohen KJ,Riccardi R,Mason W,Hargrave D,Kalambakas S,Deshpande P,Tai F,Hurh E,Geoerger B

    更新日期:2017-10-19 00:00:00