In aged mice, outgrowth of intraocular melanoma depends on proangiogenic M2-type macrophages.
Macrophages are part of the tumor microenvironment and have been associated with poor prognosis in uveal melanoma. We determined the presence of macrophages and their differentiation status in a murine intraocular melanoma model. Inoculation of B16F10 cells into the anterior chamber of the eye resulted in rapid tumor outgrowth. Strikingly, in aged mice, tumor progression depended on the presence of macrophages, as local depletion of these cells prevented tumor outgrowth, indicating that macrophages in old mice had a strong tumor-promoting role. Immunohistochemistry and gene expression analysis revealed that macrophages carried M2-type characteristics, as shown by CD163 and peroxisome proliferator-activated receptor gamma expression, and that multiple angiogenic genes were heavily overrepresented in tumors of old mice. The M2-type macrophages were also shown to have immunosuppressive features. We conclude that tumor-associated macrophages are directly involved in tumor outgrowth of intraocular melanoma and that macrophages in aged mice have a predisposition for an M2-type profile.
Ly
Long V
LV
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Baghat
Aabed
A
Versluis
Mieke
M
Jordanova
Ekaterina S
ES
Luyten
Gregorius P M
GP
van Rooijen
Nico
N
van Hall
Thorbald
T
van der Velden
Pieter A
PA
Jager
Martine J
MJ
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000276:immunology; D049109:Cell Proliferation; D004002:Clodronic Acid / Q000008:administration & dosage; D003228:Conjunctiva / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D006131:Growth Inhibitors / Q000008:administration & dosage; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology
D006131:Growth Inhibitors; D008081:Liposomes; D004002:Clodronic Acid