Macrophages are vital in spontaneous intraocular tumor eradication.
OBJECTIVE
Injection of tumor cells transformed by the early region 1 of human adenovirus type 5 (Ad5E1) in the anterior chamber (AC) of C57BL/6 mice leads to intraocular tumor formation. This tumor disappears spontaneously 3 to 4 weeks after tumor inoculation without damaging the neighboring ocular tissues. Previous studies have shown that CD4+ T cells, IFNgamma, and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) play a role in the spontaneous eradication of this particular intraocular tumor. This study was conducted to determine whether macrophages are involved in the natural elimination of this intraocular tumor.


METHODS
Ad5E1-expressing tumor cells were inoculated into the AC of syngeneic C57BL/6 mice. Macrophage depletion was obtained by subconjunctival (scj), subcutaneous (sc), or intravenous (iv) injection of clodronate liposomes 2, 8, and 14 days after tumor inoculation. Control C57BL/6 mice received PBS liposomes at similar time points after tumor injection or were left untreated. The presence of macrophages in the AC tumor was determined with the macrophage marker F4/80.


RESULTS
Progressive tumor growth was observed in mice that were subconjunctivally depleted of macrophages, whereas spontaneous tumor eradication occurred in all other groups. F4/80 staining was negative in the AC tumors of mice treated scj with clodronate liposomes in contrast to the positive F4/80 staining in the tumors of the other groups. Ad5E1 tumor antigen still reached the tumor-draining lymph nodes (DLNs) of mice locally depleted for macrophages.


CONCLUSIONS
Local macrophages in the eye are involved in the process of spontaneous AC tumor eradication in mice. However, it is not conclusive from these data exactly how tumor-specific CD4+ T cells and macrophages interact with each other to eliminate the Ad5E1-AC tumor without any collateral eye damage.
Boonman
Zita F H M
ZF
Department of Ophthalmology, Leiden University Medical Center, The Netherlands.
Schurmans
Lucas R H M
LR
van Rooijen
Nico
N
Melief
Cornelis J M
CJ
Toes
René E M
RE
Jager
Martine J
MJ
D000260:Adenoviruses, Human / Q000502:physiology; D019264:Adoptive Transfer; D000818:Animals; D000867:Anterior Chamber / Q000473:pathology*; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D004002:Clodronic Acid / Q000008:administration & dosage; D005134:Eye Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005434:Flow Cytometry; D005452:Fluoresceins; D005822:Genetic Vectors; D008081:Liposomes; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000943:Antigens, Differentiation; D005452:Fluoresceins; D008081:Liposomes; D013388:Succinimides; C036763:monocyte-macrophage differentiation antigen; D004002:Clodronic Acid