A reappraisal of macrophage polarization in glioblastoma: Histopathological and immunohistochemical findings and review of the literature.
The survival rate in glioblastoma multiforme patients has scarcely improved in the last decades; however, many new therapeutic strategies have been theorized or developed for these neoplasias. Recently, the inverse correlation observed between patient prognosis and tumor-associated macrophages (TAMs) density in solid tumors has encouraged the development of anti-tumor strategies aiming to target TAMs. As expected, TAMs polarization is influenced by both macrophage localization and tumor microenvironment signals, resulting in a more complex scenario than the simple M1/M2 activation status. Macrophage polarization in glioblastoma has not yet been fully elucidated, and most results have been obtained in experimental non-human settings, with some apparent contradiction. The authors performed a histopathological and immunohistochemical study of 37 cases of glioblastoma in order to characterize the M1 and M2 macrophage populations within TAMs. A high prevalence of CD163+ M2-polarized macrophages was detected in this cohort, whereas iNOS+ macrophages were rarely found. The down-regulation of CD68 expression in microglia/macrophage infiltrating glioblastomas is also reported for the first time. Such a finding is associated with a specific location of TAMs within the lesion, as confirmed by the fact that CD68 staining was lower than CD163, mainly in perivascular areas. The authors discuss the recent literature about the global scenario of macrophage plasticity and polarization in glioblastoma, and suggest some pivotal points for therapeutic applications.
Department of Health Science, University "Magna Græcia", Catanzaro, Italy.
Chiara
C
Mignogna
Department of Experimental and Clinical Medicine, University "Magna Græcia", Catanzaro, Italy; Hospices Civils de Lyon, hôpital Neurologique et Neurochirurgical "P. Wertheimer", Lyon-Bron, France.
Francesco
F
Signorelli
Hospices Civils de Lyon, hôpital Neurologique et Neurochirurgical "P. Wertheimer", Lyon-Bron, France.
Marco Flavio Michele
MF
Vismara
Department of Medicine and Surgery, University of Salerno, Italy.
Pio
P
Zeppa
Department of Health Science, University "Magna Græcia", Catanzaro, Italy.
Caterina
C
Camastra
Department of Experimental and Clinical Medicine, University "Magna Græcia", Catanzaro, Italy.
Tullio
T
Barni
Department of Health Science, University "Magna Græcia", Catanzaro, Italy.
Giuseppe
G
Donato
Department of Experimental and Clinical Medicine, University "Magna Græcia", Catanzaro, Italy. Electronic address: divito@unicz.it.
Anna
A
Di Vito
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D016764:Cell Polarity / Q000502:physiology*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D012189:Retrospective Studies; D059016:Tumor Microenvironment / Q000502:physiology; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
CD163; CD68; Glioblastoma multiforme; Immunosuppression; Macrophage polarization; Tumor-associated macrophages