Loic Deleyrolle

Loic Deleyrolle,

Assistant Professor

Department: MD-NEUROLOGICAL SURGERY
Business Phone: (352) 273-9381

Teaching Profile

Courses Taught
2016-2019
EGN4912 Engineering Directed Independent Research
2015
GMS7794 Neuroscience Seminar

Research Profile

DECODING BRAIN CANCER THROUGH THE LENS OF METABOLISM AND IMMUNOLOGY

OVERVIEW The overall goals of our research are to understand the complexity of brain cancer, characterize the mechanisms driving its heterogeneity and explore new treatment strategies leading to translational therapeutic development. Our laboratory has specific interests in tumor metabolism, tumor immunology, cell-cell communications and its role in driving disease presentation.

RESEARCH PROJECTS Metabolic interactions between tumor cells and the immune system in GBM: A potential Achilles heel of GBM for novel therapeutics: The glioma microenvironment is very complex and heterogeneous, a feature that impedes both the understanding of their biology as well as the elaboration of efficient clinical interventions. The focus of our proposal is to mechanistically understand the nature of the communications that take place in the tumor microenvironment, especially between immune suppressive cells and tumor cells that resist therapy but also to test the therapeutic effect of disrupting these interactions to treat brain tumors. The long-term goal of this project is to translate the information gained into strategies useful as clinical therapies improving disease outcome.

Slow cycling cell RNA based T cell therapy to prevent recurrence in GBM: The severity of glioblastoma is due to pathogenic drivers that are tolerant to conventional therapies. We have discovered a specific pool of slow-cycling cells showing greater treatment resistance and tumorigenicity. We propose to leverage our ability to purify these cells to develop a novel targeted immunotherapy strategy based on the use of immunogenic antigens isolated from these clinically relevant population of cells as activator of immune effectors in the context of adoptive cell therapy to prevent recurrence in GBM.

Potentiating T cell anti-tumor efficiency via metabolic reprogramming for adoptive cellular immunotherapy to treat brain cancer: GBM are a challenge for neuro-oncologists and current therapies are minimally effective. Standard-of-care treatment is almost inevitably followed by disease recurrence. Adoptive T cell transfer has emerged as a viable therapeutic for brain malignancies. While promising, the efficacy of this approach is often limited by a complex immunosuppressive tumor microenvironment. These complexities mean that more sophisticated T cell products are required. T cells undergo metabolic reprogramming upon activation marked by an increased glucose uptake. This project proposes to test a new approach based on reprograming the metabolic qualities of anti-tumor immune cells to enhance immunotherapy for the treatment of GBM. We hypothesize that brain tumor cells outcompete host or adoptively transferred T cells for metabolic substrates like glucose, directly limiting their function and supporting tumor progression. This project examines the effect of enhancing T cell glucose metabolism through genetic manipulation, in vitro metabolic conditioning in mouse models of GBM and using patient-based platforms.

Co-opting TME lactate signal to benefit T cell therapy: Complex alterations of energy pathways have been described in cancers and originate from the Warburg hypothesis, which postulates that the majority of cancer cells derive their energy from aerobic glycolysis. This specific metabolic reprogramming of strong engagement in the glycolytic pathway is a hallmark of glioblastoma (GBM). As part of their high glycolytic rate, GBM secrete metabolic byproducts such as lactate, which acts as an important oncometabolite and immunosuppressor. Capitalizing on our current knowledge of tumor metabolism and how metabolic pathways affect immune response, the goal of this project is to test an innovative therapeutic modality based on reprograming the metabolic qualities of anti-tumor immune cells to enhance immunotherapy for the treatment of GBM. We hypothesize that co-opting lactate signal may be a useful approach to overcome metabolically driven tumor-imposed immunosuppression and for developing efficient immunotherapies. This project investigates the efficacy of lactate receptor genetic engineering in T cells in the context of adoptive cell therapy to treat GBM.

Areas of Interest
  • Brain Tumors
  • Cancer Immunotherapy
  • Immunometabolism
  • Role and potential of neural stem cells in brain tumors
Open Researcher and Contributor ID (ORCID)

0000-0002-1129-744X

Publications

2022
Slow-Cycling Cells in Glioblastoma: A Specific Population in the Cellular Mosaic of Cancer Stem Cells
Cancers. 14(5) [DOI] 10.3390/cancers14051126. [PMID] 35267434.
2022
Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity.
Frontiers in oncology. 12 [DOI] 10.3389/fonc.2022.837589. [PMID] 35359402.
2021
HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells.
Cancers. 13(7) [DOI] 10.3390/cancers13071644. [PMID] 33915983.
2021
Metabolomics Monitoring of Treatment Response to Brain Tumor Immunotherapy.
Frontiers in oncology. 11 [DOI] 10.3389/fonc.2021.691246. [PMID] 34150663.
2020
Adult immuno-oncology: using past failures to inform the future.
Neuro-oncology. 22(9):1249-1261 [DOI] 10.1093/neuonc/noaa116. [PMID] 32391559.
2020
Dysregulation of Glutamate Transport Enhances Treg Function That Promotes VEGF Blockade Resistance in Glioblastoma
Cancer Research. 80(3):499-509 [DOI] 10.1158/0008-5472.can-19-1577.
2020
Metabolic heterogeneity and adaptability in brain tumors
Cellular and Molecular Life Sciences. 77(24):5101-5119 [DOI] 10.1007/s00018-020-03569-w. [PMID] 32506168.
2019
CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.
Nature communications. 10(1) [DOI] 10.1038/s41467-019-11869-4. [PMID] 31488817.
2018
Infiltrative and drug‐resistant slow‐cycling cells support metabolic heterogeneity in glioblastoma
The EMBO Journal. 37(23) [DOI] 10.15252/embj.201798772. [PMID] 30322894.
2018
Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy.
Nano letters. 18(10):6195-6206 [DOI] 10.1021/acs.nanolett.8b02179. [PMID] 30259750.
2018
Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System.
Scientific reports. 8(1) [DOI] 10.1038/s41598-018-21927-4. [PMID] 29476107.
2018
Using Carboxy Fluorescein Succinimidyl Ester (CFSE) to Identify Quiescent Glioblastoma Stem-Like Cells.
Methods in molecular biology (Clifton, N.J.). 1686:59-67 [DOI] 10.1007/978-1-4939-7371-2_4. [PMID] 29030812.
2017
Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.
International journal of cancer. 141(7):1434-1444 [DOI] 10.1002/ijc.30830. [PMID] 28612394.
2016
A Supplemented High-Fat Low-Carbohydrate Diet for the Treatment of Glioblastoma.
Clinical cancer research : an official journal of the American Association for Cancer Research. 22(10):2482-95 [DOI] 10.1158/1078-0432.CCR-15-0916. [PMID] 26631612.
2016
Disruption of KIF3A in patient-derived glioblastoma cells: effects on ciliogenesis, hedgehog sensitivity, and tumorigenesis.
Oncotarget. 7(6):7029-43 [DOI] 10.18632/oncotarget.6854. [PMID] 26760767.
2016
PCM1 Depletion Inhibits Glioblastoma Cell Ciliogenesis and Increases Cell Death and Sensitivity to Temozolomide.
Translational oncology. 9(5):392-402 [DOI] 10.1016/j.tranon.2016.08.006. [PMID] 27661404.
2016
Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels.
Scientific reports. 6 [DOI] 10.1038/srep31915. [PMID] 27549983.
2016
Tayloring cell populations for neurodegenerative diseases.
Neural regeneration research. 11(10):1582-1583 [PMID] 27904487.
2016
Transplantation of Defined Populations of Differentiated Human Neural Stem Cell Progeny.
Scientific reports. 6 [DOI] 10.1038/srep23579. [PMID] 27030542.
2015
Constitutive activation of myosin-dependent contractility sensitizes glioma tumor-initiating cells to mechanical inputs and reduces tissue invasion.
Cancer research. 75(6):1113-22 [DOI] 10.1158/0008-5472.CAN-13-3426. [PMID] 25634210.
2015
Differential connexin function enhances self-renewal in glioblastoma.
Cell reports. 11(7):1031-42 [DOI] 10.1016/j.celrep.2015.04.021. [PMID] 25959821.
2015
Neurosphere and adherent culture conditions are equivalent for malignant glioma stem cell lines.
Anatomy & cell biology. 48(1):25-35 [DOI] 10.5115/acb.2015.48.1.25. [PMID] 25806119.
2015
OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.
PloS one. 10(4) [DOI] 10.1371/journal.pone.0122337. [PMID] 25875008.
2014
Detection of primary cilia in human glioblastoma.
Journal of neuro-oncology. 117(1):15-24 [DOI] 10.1007/s11060-013-1340-y. [PMID] 24510433.
2014
Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support.
Frontiers in cellular neuroscience. 8 [DOI] 10.3389/fncel.2014.00180. [PMID] 25076873.
2014
Multiplex mapping of chromatin accessibility and DNA methylation within targeted single molecules identifies epigenetic heterogeneity in neural stem cells and glioblastoma.
Genome research. 24(2):329-39 [DOI] 10.1101/gr.161737.113. [PMID] 24105770.
2013
Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma.
Future oncology (London, England). 9(9):1389-96 [DOI] 10.2217/fon.13.96. [PMID] 23980685.
2013
Gap Junction Switching Maintains the Tumor Hierarchy in Glioblastoma
Neuro-Oncology. 15(3):210-211
2013
The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance.
EMBO molecular medicine. 5(8):1196-212 [DOI] 10.1002/emmm.201302827. [PMID] 23818228.
2012
High-throughput chemical screens identify disulfiram as an inhibitor of human glioblastoma stem cells.
Oncotarget. 3(10):1124-36 [PMID] 23165409.
2012
Identification and isolation of slow-dividing cells in human glioblastoma using carboxy fluorescein succinimidyl ester (CFSE).
Journal of visualized experiments : JoVE. (62) [DOI] 10.3791/3918. [PMID] 22565048.
2011
Determination of somatic and cancer stem cell self-renewing symmetric division rate using sphere assays.
PloS one. 6(1) [DOI] 10.1371/journal.pone.0015844. [PMID] 21246056.
2011
Evidence for label-retaining tumour-initiating cells in human glioblastoma.
Brain : a journal of neurology. 134(Pt 5):1331-43 [DOI] 10.1093/brain/awr081. [PMID] 21515906.
2011
Isolation and characterization of adult neural stem cells.
Methods in molecular biology (Clifton, N.J.). 750:61-77 [DOI] 10.1007/978-1-61779-145-1_4. [PMID] 21618083.
2011
Isolation and expansion of human glioblastoma multiforme tumor cells using the neurosphere assay.
Journal of visualized experiments : JoVE. (56) [DOI] 10.3791/3633. [PMID] 22064695.
2011
Purification of immature neuronal cells from neural stem cell progeny.
PloS one. 6(6) [DOI] 10.1371/journal.pone.0020941. [PMID] 21687800.
2011
The cancer stem cell hypothesis: failures and pitfalls.
Neurosurgery. 68(2):531-45; discussion 545 [DOI] 10.1227/NEU.0b013e3181ff9eb5. [PMID] 21135745.
2011
The origins of glioma: E Pluribus Unum?
Glia. 59(8):1135-47 [DOI] 10.1002/glia.21143. [PMID] 21351156.
2011
Y-Box Binding Protein-1 (Yb-1) Inhibition Triggers Differentiation of Normal and Cancer Stem Cells From the Brain
Neuro-Oncology. 13
2011
YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth.
Cancer research. 71(16):5569-78 [DOI] 10.1158/0008-5472.CAN-10-2805. [PMID] 21730024.
2010
Circulating Tumor Cells (Ctcs) in Patients With Glioblastoma Multiforme (Gbm)
Neuro-Oncology. 12
2009
Identifying and enumerating neural stem cells: application to aging and cancer.
Progress in brain research. 175:43-51 [DOI] 10.1016/S0079-6123(09)17504-0. [PMID] 19660648.
2009
Isolation, expansion, and differentiation of adult Mammalian neural stem and progenitor cells using the neurosphere assay.
Methods in molecular biology (Clifton, N.J.). 549:91-101 [DOI] 10.1007/978-1-60327-931-4_7. [PMID] 19378198.
2008
Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro.
Journal of neuroscience research. 86(9):1916-26 [DOI] 10.1002/jnr.21646. [PMID] 18335522.
2008
Enumeration of neural stem and progenitor cells in the neural colony-forming cell assay.
Stem cells (Dayton, Ohio). 26(4):988-96 [DOI] 10.1634/stemcells.2007-0867. [PMID] 18218818.
2008
The neurosphere assay, a method under scrutiny.
Acta neuropsychiatrica. 20(1):2-8 [DOI] 10.1111/j.1601-5215.2007.00251.x. [PMID] 26953088.
2003
The human NTERA2 neural cell line generates neurons on growth under neural stem cell conditions and exhibits characteristics of radial glial cells.
Molecular and cellular neurosciences. 24(1):198-213 [PMID] 14550780.
Slow-cycling cells in glioblastoma: a specific population in the cellular mosaic of cancer stem cells
. [DOI] 10.1101/2022.01.25.477703.

Grants

Apr 2022 ACTIVE
SPDYE3, A Novel Cancer Testis (CT) Antigen for Glioma Immunotherapy
Role: Co-Investigator
Funding: NATL INST OF HLTH NCI
Apr 2022 ACTIVE
Co-opting TME lactate signal to benefit T cell therapy
Role: Principal Investigator
Funding: FL DEPT OF HLTH LIVE LIKE BELLA
May 2021 ACTIVE
Targeting Oligodendrogliomas with LAIR1/CD305 Blockade
Role: Co-Investigator
Funding: OLIGO NATION
Feb 2021 ACTIVE
Slow?cycling?cell?RNA?based?T?cell?therapy?to?prevent?recurrence?in?GBM?
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Jul 2019 – Mar 2021
Engineering T cell metabolic fitness to treat pediatric brain tumors
Role: Principal Investigator
Funding: ST BALDRICKS FOUNDATION
Jul 2018 ACTIVE
Florida Center for Brain Tumor Research
Role: Project Manager
Funding: FL DEPT OF HLTH
Jun 2018 – Sep 2019
Targeting glioma slow-cycling cells using autologous dendritic cell vaccine
Role: Principal Investigator
Funding: AMER BRAIN TUMOR ASSOCIATION
Jul 2016 ACTIVE
Metabolic Characterization and Targeting of Slow-Cycling Glioma Stem Cells
Role: Principal Investigator
Funding: UF FOUNDATION
Feb 2015 ACTIVE
UF Health Cancer Center Pilot Project Grants funded through the Florida Consortium of National Cancer Institute Centers Program
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Jul 2013 – Jun 2021
Florida Center for Brain Tumor Research – Statewide Brain Tumor Registry Program at the McKnight Brain Institute
Role: Project Manager
Funding: FL DEPT OF HLTH
Mar 2013 ACTIVE
Support for brain tumor research
Role: Faculty
Funding: UF FOUNDATION
Jan 2012 – Dec 2016
Institutional Research Grant
Role: Project Manager
Funding: AMER CANCER SOC

Contact Details

Phones:
Business:
(352) 273-9381
Addresses:
Business Mailing:
PO BOX 100265
DEPARTMENT OF NEUROSURGERY
GAINESVILLE FL 326100265
Business Street:
1333 CENTER DR RM B1 126
BASIC SCIENCE BLDG
GAINESVILLE FL 32610