title: Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part 1: stimulatory effects on blood monocytes and monocyte-derived cells of the brain.
abstract: OBJECTIVE
  Immunotherapy with immunostimulants is an attractive therapy against gliomas. C-type lectin receptors specific for galactose/N-acetylgalactosamine (GCLR) regulate cellular differentiation, recognition, and trafficking of monocyte-derived cells. A peptide mimetic of GCLR ligands (GCLRP) was used to activate blood monocytes and populations of myeloid-derived cells against a murine glioblastoma.
  
  
  METHODS
  The ability of GCLRP to stimulate phagocytosis by human microglia and monocyte-derived cells of the brain (MDCB) isolated from a human glioblastoma was initially assessed in vitro. Induction of activation markers on blood monocytes was assayed by flow cytometry after administration of GCLRP to naive mice. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells and were randomized for tumor size by magnetic resonance imaging, which was also used to assess increase in tumor size. Brain tumor tissues were analyzed using flow cytometry, histology, and enzyme-linked immunosorbent assay with respect to tumor, peritumoral area, and contralateral hemisphere regions.
  
  
  RESULTS
  GCLRP exhibited strong stimulatory effect on MDCBs and blood monocytes in vitro and in vivo. GCLRP was associated with an increased percentage of precursors of dendritic cells in the blood (P = 0.003), which differentiated into patrolling macrophages in tumoral (P = 0.001) and peritumoral areas (P = 0.04), rather than into dendritic cells, as in control animals. Treatment with GCLRP did not result in a significant change in survival of mice bearing a tumor.
  
  
  CONCLUSIONS
  In vitro and in vivo activation of monocytes was achieved by administration of GCLR to mice. GCLRP-activated blood monocytes were recruited to the brain and exhibited specific phenotypes corresponding with tumor region (glioma, peritumoral zone, and contralateral glioma-free hemisphere). GCLRP treatment alone was associated with increased glioma mass as the result of the infiltration of phagocytic cells. Regional specificity for MDCB may have significant tumor treatment implications.
authors.affiliation: Neurosurgery Research Laboratory, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix.
authors.forename: Sergiy V
authors.initials: SV
authors.lastname: Kushchayev
authors.forename: Tejas
authors.initials: T
authors.lastname: Sankar
authors.forename: Laura L
authors.initials: LL
authors.lastname: Eggink
authors.forename: Yevgeniya S
authors.initials: YS
authors.lastname: Kushchayeva
authors.forename: Philip C
authors.initials: PC
authors.lastname: Wiener
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Hoober
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eschbacher
authors.forename: Ruolan
authors.initials: R
authors.lastname: Liu
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.forename: Mohammed G
authors.initials: MG
authors.lastname: Abdelwahab
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Scheck
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul