Journal Articles

Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR

To delineate the relative contribution of multiple HLA alleles to peptide editing by the intracellular MHC chaperone TAPBPR, Ilca et al. evaluated TAPBPR binding to HLA on beads and on cell surfaces, peptide editing on cellular surfaces, and binding/editing of targeted HLA mutations. HLA-A, in particular HLA-A2 and -A24 supertypes, were significantly more impacted by TAPBPR than HLA-B/C or other HLA-A family members. This preferential binding/editing was strongly associated with H114 and Y116 in the anchor residue binding F pocket of HLA. Allele-specific preferential editing may have implications for sensitivity to disease.

To delineate the relative contribution of multiple HLA alleles to peptide editing by the intracellular MHC chaperone TAPBPR, Ilca et al. evaluated TAPBPR binding to HLA on beads and on cell surfaces, peptide editing on cellular surfaces, and binding/editing of targeted HLA mutations. HLA-A, in particular HLA-A2 and -A24 supertypes, were significantly more impacted by TAPBPR than HLA-B/C or other HLA-A family members. This preferential binding/editing was strongly associated with H114 and Y116 in the anchor residue binding F pocket of HLA. Allele-specific preferential editing may have implications for sensitivity to disease.

Understanding how peptide selection is controlled on different major histocompatibility complex class I (MHC I) molecules is pivotal for determining how variations in these proteins influence our predisposition to infectious diseases, cancer, and autoinflammatory conditions. Although the intracellular chaperone TAPBPR edits MHC I peptides, it is unclear which allotypes are subjected to TAPBPR-mediated peptide editing. Here, we examine the ability of 97 different human leukocyte antigen (HLA) class I allotypes to interact with TAPBPR. We reveal a striking preference of TAPBPR for HLA-A, particularly for supertypes A2 and A24, over HLA-B and -C molecules. We demonstrate that the increased propensity of these HLA-A molecules to undergo TAPBPR-mediated peptide editing is determined by molecular features of the HLA-A F pocket, specifically residues H114 and Y116. This work reveals that specific polymorphisms in MHC I strongly influence their susceptibility to chaperone-mediated peptide editing, which may play a significant role in disease predisposition.

Author Info: (1) Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. (2) Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104 Freiburg,

Author Info: (1) Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. (2) Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104 Freiburg, Germany. (3) Tissue Typing Laboratory, Box 209, Level 6 ATC, Cambridge University Hospitals, NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK. (4) Tissue Typing Laboratory, Box 209, Level 6 ATC, Cambridge University Hospitals, NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK. (5) Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. Electronic address: lhb22@cam.ac.uk.

Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features. We identify five DNA methylation subgroups associated with anatomical sites and SMARCB1 mutation patterns. Groups 1, 3, and 4 exhibit cytotoxic T cell infiltration and expression of immune checkpoint regulators, consistent with a potential role for immunotherapy in rhabdoid tumor patients.

Author Info: (1) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (2) Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neu

Author Info: (1) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (2) Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. (3) Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada. (4) Department of Molecular Genetics, DKFZ, Heidelberg 69120, Germany. (5) Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. (6) Center for Digital Health, Berlin Institute of Health and Charite-Universitatsmedizin Berlin, Berlin 10117, Germany; Heidelberg Center for Personalized Oncology, DKFZ, Heidelberg 69120, Germany. (7) Department of Molecular Genetics, DKFZ, Heidelberg 69120, Germany. (8) Hopp Children's Cancer Center, Heidelberg 69120, Germany. (9) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (10) Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3N1, Canada. (11) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (12) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (13) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (14) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (15) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (16) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (17) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (18) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (19) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada. (20) Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. (21) Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. (22) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada. (23) Hopp Children's Cancer Center, Heidelberg 69120, Germany. (24) Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry; and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg 97074, Germany. (25) Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster 48149, Germany. (26) Institute of Neuropathology, University Hospital Muenster, Muenster 48149, Germany. (27) University Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg 86156, Germany. (28) Department of Pathology and Laboratory Medicine, Lurie Children's Hospital, Northwestern University's Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, IL 60611, USA. (29) Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 3E6, Canada. (30) Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany. (31) Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada. Electronic address: mmarra@bcgsc.ca. (32) Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany. Electronic address: m.kool@kitz-heidelberg.de.

Galectin-1-driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs.

Author Info: (1) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (2) Department of Radiation Oncology, University of Texas Southwestern, Dal

Author Info: (1) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (2) Department of Radiation Oncology, University of Texas Southwestern, Dallas, Texas, USA. (3) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (4) Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. (5) Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. (6) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (7) Biologics Discovery California, Bristol-Myers Squibb, Redwood City, California, USA. (8) Biologics Discovery California, Bristol-Myers Squibb, Redwood City, California, USA. (9) Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. (10) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (11) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (12) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (13) Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. (14) Biologics Discovery California, Bristol-Myers Squibb, Redwood City, California, USA. (15) Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), Bethesda, Maryland, USA. (16) Department of Surgery - Otolaryngology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA. (17) Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. (18) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA. (19) Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.

Cancer immunotherapy needs to learn how to stick to its guns

Cancer immunotherapy and its budding effectiveness at improving patient outcomes has revitalized our hope to fight cancer in a logical and safe manner. Immunotherapeutic approaches to reengage the immune system have largely focused on reversing immune checkpoint inhibitor pathways, which suppress the antitumor response. Although these approaches have generated much excitement, they still lack absolute success. Interestingly, newly described host-tumor sugar chains (glycosylations) and glycosylation-binding proteins (lectins) play key roles in evading the immune system to determine cancer progression. In this issue of the JCI, Nambiar et al. used patient head and neck tumors and a mouse model system to investigate the role of galactose-binding lectin 1 (Gal1) in immunotherapy resistance. The authors demonstrated that Gal1 can affect immune checkpoint inhibitor therapy by increasing immune checkpoint molecules and immunosuppressive signaling in the tumor. Notably, these results suggest that targeting a tumor's glycobiological state will improve treatment efficacy.

Author Info: (1) (2)

Author Info: (1) (2)

Destress and do not suppress: targeting adrenergic signaling in tumor immunosuppression

Tumor-induced immunosuppression is a common obstacle for cancer treatment. Adrenergic signaling triggered by chronic stress participates in the creation of an immunosuppressive microenvironment by promoting myeloid-derived suppressor cell (MDSC) proliferation and activation. In this issue of the JCI, Mohammadpour et al. elegantly delve into the mechanisms underlying MDSC contribution to tumor development. They used in vitro and in vivo mouse models to demonstrate that chronic stress results in MDSC accumulation, survival, and immune-inhibitory activity. Of therapeutic relevance, the authors showed that propranolol, a commonly prescribed beta-blocker, can reduce MDSC immunosuppression and enhance the effect of other cancer therapies.

Author Info: (1) Navarra's Health Research Institute (IDISNA) Pamplona, Spain. Program in Solid Tumors, Foundation for Applied Medical Research, Pamplona, Spain. Department of Pediatrics, Unive

Author Info: (1) Navarra's Health Research Institute (IDISNA) Pamplona, Spain. Program in Solid Tumors, Foundation for Applied Medical Research, Pamplona, Spain. Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain. (2) Navarra's Health Research Institute (IDISNA) Pamplona, Spain. Program in Solid Tumors, Foundation for Applied Medical Research, Pamplona, Spain. Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.

Development of molecular and pharmacological switches for chimeric antigen receptor T cells

The use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome. While several avenues are being pursued to limit the off-target effects, it is critically important that any intervention strategy has minimal consequences on long term efficacy. A recent study published in Science Translational Medicine by Dr. Hudecek's group proved that dasatinib, a tyrosine kinase inhibitor, can serve as an on/off switch for CD19-CAR-T cells in preclinical models by limiting toxicities while maintaining therapeutic efficacy. In this editorial, we discuss the recent strategies for generating safer CAR-T cells, and also important questions surrounding the use of dasatinib for emergency intervention of CAR-T cell mediated cytokine release syndrome.

Author Info: (1) Division of Medical Oncology, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA.0000 0001 2285 7943grid.261

Author Info: (1) Division of Medical Oncology, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA.0000 0001 2285 7943grid.261331.4 (2) Division of Medical Oncology, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA.0000 0001 2285 7943grid.261331.4 (3) Division of Medical Oncology, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA.0000 0001 2285 7943grid.261331.4 (4) Division of Medical Oncology, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 USA.0000 0001 2285 7943grid.261331.4

The Common Costimulatory and Coinhibitory Signaling Molecules in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinomas (HNSCCs) are closely linked with immunosuppression, accompanied by complex immune cell functional activities. The abnormal competition between costimulatory and coinhibitory signal molecules plays an important role in the malignant progression of HNSCC. This review will summarize the features of costimulatory molecules (including CD137, OX40 as well as CD40) and coinhibitory molecules (including CTLA-4, PD-1, LAG3, and TIM3), analyze the underlying mechanism behind these molecules' regulation of the progression of HNSCC, and introduce the clinic application. Vaccines, such as those targeting STING while working synergistically with monoclonal antibodies, are also discussed. A deep understanding of the tumor immune landscape will help find new and improved tumor immunotherapy for HNSCC.

Author Info: (1) State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Si

Author Info: (1) State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. (2) State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. (3) State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. (4) State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China. (5) State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Pan-Cancer Analysis Reveals Disrupted Circadian Clock Associates With T Cell Exhaustion

Although dysfunctional circadian clock has emerged as a hallmark of cancer, fundamental gaps remain in our understanding of the underlying mechanisms involved. Here, we systematically analyze the core genes of the circadian clock (CLOCK, ARNTL, ARNTL2, NPAS2, NR1D1, NR1D2, CRY1, CRY2, RORA, RORB, RORC, PER1, PER2, and PER3) across a broad range of cancers. To our surprise, core negative regulators (PER1, PER2, PER3, CRY1, and CRY2) are consistently downregulated, while core positive regulators show minimal alterations, indicating disrupted circadian clock in cancers. Such downregulation originates from copy number variations where heterozygous deletion predominates. The disrupted circadian clock is significantly associated with patient outcome. Further pathway enrichment analysis suggests that the circadian clock widely impacts 45 pathways such as the Ras signaling pathway and T cell receptor signaling pathway. By using state-of-the-art immune cell deconvolution and pathway quantification, we demonstrate that abnormal circadian clock contributes to T cell exhaustion and global upregulation of immune inhibitory molecules such as PD-L1 and CTLA-4. In summary, the rhythm of the circadian clock is disrupted in cancers. Abnormal circadian clock linked with immune evasion may serve as a potential hallmark of cancer.

Author Info: (1) Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, China. (2) Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, China

Author Info: (1) Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, China. (2) Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, China. Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China. (3) Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China. (4) Laboratory of Medical Science, School of Medicine, Nantong University, Jiangsu, China. Department of Immunology, School of Medicine, Nantong University, Jiangsu, China. (5) Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China.

Targeting Macrophages: Friends or Foes in Disease

Macrophages occupy a prominent position during immune responses. They are considered the final effectors of any given immune response since they can be activated by a wide range of surface ligands and cytokines to acquire a continuum of functional states. Macrophages are involved in tissue homeostasis and in the promotion or resolution of inflammatory responses, causing tissue damage or helping in tissue repair. Knowledge in macrophage polarization has significantly increased in the last decade. Biomarkers, functions, and metabolic states associated with macrophage polarization status have been defined both in murine and human models. Moreover, a large body of evidence demonstrated that macrophage status is a dynamic process that can be modified. Macrophages orchestrate virtually all major diseases-sepsis, infection, chronic inflammatory diseases (rheumatoid arthritis), neurodegenerative disease, and cancer-and thus they represent attractive therapeutic targets. In fact, the possibility to "reprogram" macrophage status is considered as a promising strategy for designing novel therapies. Here, we will review the role of different tissue macrophage populations in the instauration and progression of inflammatory and non-inflammatory pathologies, as exemplified by rheumatoid arthritis, osteoporosis, glioblastoma, and tumor metastasis. We will analyze: 1) the potential as therapeutic targets of recently described macrophage populations, such as osteomacs, reported to play an important role in bone formation and homeostasis or metastasis-associated macrophages (MAMs), key players in the generation of premetastatic niche; 2) the current and potential future approaches to target monocytes/macrophages and their inflammation-causing products in rheumatoid arthritis; and 3) the development of novel intervention strategies using oncolytic viruses, immunomodulatory agents, and checkpoint inhibitors aiming to boost M1-associated anti-tumor immunity. In this review, we will focus on the potential of macrophages as therapeutic targets and discuss their involvement in state-of-the-art strategies to modulate prevalent pathologies of aging societies.

Author Info: (1) Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, Madrid, Spain. (2) IMDEA Nanoscience Institute, Madrid, Spain. Fundacion de Investigacion H

Author Info: (1) Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, Madrid, Spain. (2) IMDEA Nanoscience Institute, Madrid, Spain. Fundacion de Investigacion HM Hospitales, Madrid, Spain. (3) Department I for Internal Medicine and CECAD, University Hospital of Cologne, Cologne, Germany. (4) Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, Madrid, Spain. (5) Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, Madrid, Spain. (6) Department of Basic Medical Sciences, Faculty of Medicine, San Pablo CEU University, Madrid, Spain.

Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors

Rhabdoid tumors (RTs) are genomically simple pediatric cancers driven by the biallelic inactivation of SMARCB1, leading to SWI/SNF chromatin remodeler complex deficiency. Comprehensive evaluation of the immune infiltrates of human and mice RTs, including immunohistochemistry, bulk RNA sequencing and DNA methylation profiling studies showed a high rate of tumors infiltrated by T and myeloid cells. Single-cell RNA (scRNA) and T cell receptor sequencing highlighted the heterogeneity of these cells and revealed therapeutically targetable exhausted effector and clonally expanded tissue resident memory CD8(+) T subpopulations, likely representing tumor-specific cells. Checkpoint blockade therapy in an experimental RT model induced the regression of established tumors and durable immune responses. Finally, we show that one mechanism mediating RTs immunogenicity involves SMARCB1-dependent re-expression of endogenous retroviruses and interferon-signaling activation.

Author Info: (1) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department,

Author Info: (1) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (2) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (3) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (4) Sainte-Anne Hospital, Department of Neuropathology, Paris, France. (5) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (6) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (7) AP-HP, Necker Hospital, Department of Neurosurgery, Paris, France. (8) PSL Research University, Institut Curie Research Center, INSERM U900, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France. (9) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (10) PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (11) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (12) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (13) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (14) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (15) PSL Research University, Institut Curie Hospital, Laboratory of Somatic Genetics, Paris, France. (16) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (17) PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France. (18) PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France. (19) PSL Research University, Institut Curie Genomics of Excellence (ICGex) Platform, Paris, France. (20) PSL Research University, Institut Curie Research Center, CNRS UMR 3347, INSERM U1021, Orsay, France. (21) AP-HP, Armand Trousseau Hospital, Department of Pathology, Paris, France. (22) AP-HP, Necker Hospital, Department of Pathology, Paris, France. (23) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (24) PSL Research University, Institut Curie Research Center, INSERM U900, Paris, France; MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France. (25) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (26) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (27) AP-HP, Necker Hospital, Department of Neurosurgery, Paris, France. (28) PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. (29) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. (30) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France. Electronic address: joshua.waterfall@curie.fr. (31) PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; PSL Research University, Institut Curie Research Center, INSERM U932, Paris, France. Electronic address: eliane.piaggio@curie.fr. (32) PSL Research University, Institut Curie Research Center, INSERM U830, Paris, France; PSL Research University, Institut Curie Research Center, Translational Research Department, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France. Electronic address: franck.bourdeaut@curie.fr.

Close Modal

Small change for you. Big change for us!

This Thanksgiving season, show your support for cancer research by donating your change.

In less than a minute, link your credit card with our partner RoundUp App.

Every purchase you make with that card will be rounded up and the change will be donated to ACIR.

All transactions are securely made through Stripe.