title: The brain tissue response to surgical injury and its possible contribution to glioma recurrence.
abstract: Surgery is the first line therapy for glioma. However, glioma recurs in 90 % of the patients in the resection margin. The impact of surgical brain injury (SBI) on glioma recurrence is largely overlooked. Herein, we review some of the mechanisms involved in tissue repair that may impact glioma recurrence at the resection margin. Many processes or molecules involved in tissue repair after brain injury are also critical for glioma growth. They include a wide array of secreted growth factors, cytokines and transcription factors including NFКB and STAT3 which in turn activate proliferative and anti-apoptotic genes and processes such as angiogenesis and inflammation. Because some residual glioma cells always remain in the tumor resection margin, there are now compelling arguments to suggest that some aspects of the brain tissue response to SBI can also participate to glioma recurrence at the resection margin. Brain tissue response to SBI recruits angiogenesis and inflammation that precede and then follow tumor recurrence at the resection margin. The healing response to SBI is double edged, as inflammation is involved in regeneration and healing, and has both pro- and anti-tumorigenic functions. A promising therapeutic approach is to normalize and re-educate the molecular and cellular responses at the resection margin to promote anti-tumorigenic processes involved in healing while inhibiting pro-tumorigenic activities. Manipulation of the inflammatory response to SBI to prevent local recurrence could also enhance the efficacy of other therapies such as immunotherapy. However, our current knowledge is far from sufficient to achieve this goal. Acknowledging, understanding and manipulating the double-edged role played by SBI in glioma recurrence is surely challenging, but it cannot be longer delayed.
authors.affiliation: INSERM UA 01, Clinatec, Centre de recherche biomédicale Edmond J. Safra, CEA 17 rue des Martyrs, 38054, Grenoble cedex, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Hamard
authors.affiliation: Clinatec, CEA Leti, Grenoble, France.
authors.forename: David
authors.initials: D
authors.lastname: Ratel
authors.affiliation: INSERM UA 01, Clinatec, Centre de recherche biomédicale Edmond J. Safra, CEA 17 rue des Martyrs, 38054, Grenoble cedex, France.|Clinique de neurochirurgie, CHU de Grenoble, Grenoble, France.|INSERM UMR 1205, bâtiment modulaire 40-23, CEA, 17 rue des Martyrs, 38054, Grenoble, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Selek
authors.affiliation: INSERM UA 01, Clinatec, Centre de recherche biomédicale Edmond J. Safra, CEA 17 rue des Martyrs, 38054, Grenoble cedex, France.|CHU de Grenoble, Grenoble, France.|Université Joseph Fourier, B.P. 217, 38043, Grenoble cedex 09, France.|INSERM UMR 1205, bâtiment modulaire 40-23, CEA, 17 rue des Martyrs, 38054, Grenoble, France.|Université Grenoble Alpes, 38043, Grenoble cedex 09, France.
authors.forename: François
authors.initials: F
authors.lastname: Berger
authors.affiliation: INSERM UA 01, Clinatec, Centre de recherche biomédicale Edmond J. Safra, CEA 17 rue des Martyrs, 38054, Grenoble cedex, France.|INSERM UMR 1205, bâtiment modulaire 40-23, CEA, 17 rue des Martyrs, 38054, Grenoble, France.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Sanden
authors.affiliation: INSERM UA 01, Clinatec, Centre de recherche biomédicale Edmond J. Safra, CEA 17 rue des Martyrs, 38054, Grenoble cedex, France. didier.wion@ujf-grenoble.fr.|INSERM UMR 1205, bâtiment modulaire 40-23, CEA, 17 rue des Martyrs, 38054, Grenoble, France. didier.wion@ujf-grenoble.fr.
authors.forename: Didier
authors.identifier: 0000-0001-7144-6470
authors.initials: D
authors.lastname: Wion
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000601:surgery*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000601:surgery*; D005910:Glioma / Q000378:metabolism* / Q000601:surgery*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control; D019635:Neurosurgical Procedures / Q000009:adverse effects
keywords: Dormancy; Glioma; Inflammation; Microenvironment; Surgery; Wound healing