Studies On Intraocular Allogenic Melanomas And Associated Immune Deviation In Mice

Uveal melanoma is a tumor with a high incidenee of metastasis and ahigh mortality rate. To control the intraocular tuWr and make aneffective treatment of metastases, further research oll itS pathogenesis isnecessary. There is a special relation betWeen uveal melanoma andimmune system, but it is hard to observe the immune resPOnse on patientsin vivo for lacking of proper method. Establishing animal models withintraocular melanoma is a valuable way.There may be immune privilege in eye fOr intracular tUmors.Allogenic tumors inoculated into anterior chamber of the eye in micewere able to result in progressively growing intraocular tUmors andimPaired delayed-type hyPersensitivity (DTH) reaCtivity, but produeednormal humoral antibodies and cytotoxic T cells sPecific for melanomacells. By contrast, subcutaneous inoculation of melanoma cells inducedsignificant DTH resPonses tO the alloantigens expressed on the tumorcells and stimulated brisk rejection of the subcutaneously injected tumorcells. This pattern of immunological impairment has been termed anteriorchamber-associated immune deviation (ACAID) by Streilein in 1980s. Itis not clear whether this phenomenon exists in vitreous cavity (VC).The immune privilege in eye for intraocular tumor is able to beabrogated. Intraocular tumors growing is owing to ACAID, but it will berejected when the ACAlD disaPPear such as aPpropriately timedsplenectomy. Therefore, theraPeutic protocols using sPecificimmunization are able to be devised to induce hosts bearing intraoculartumors to mount immune response very vigorously tO destroy the tumorin the eye, and sufficiently precise to preserve the fUnctional andanatomic integrity of the eye precisely.Our research mainly observed whether allogeneic intraocularmelanoma could induce ACAlD and vitreous cavity-associated inunnedeviation (VCAlD) in Kunming ndce. If it could, what effect will befound in hosts bearing intraocuar tumors when the associated immunedeviation was abrogated and tumor cell vaCCine was aPPlied.Part I Establishing Intraocular Mclanoma modeIs in MicePURPOSE. To Establish an allogenic intraocular melanoma model inMice fOr stUding immune privilege of eyes.METHODS. Allogeneic melanoma cells B16F10 (C57BU6) wasinoculated into anterior chamber (AC or vitreous cavity (VC) orsubcutaneous (SC) in Kunming mice with three groups. The tumorgrowing status were observed by slip-lamP biomicroscopy and operatingmicroscopy for 32 days. The incidence of tumor and time of eyeballdiabrosis and size of the tumor were recorded fOr statistics analysis.Pathological examination was given for tumors at last.RESULTS. 1. The incidence of tumor in both AC grouP (12/12 eyes)and VC grouP (12/12 eyes) was higher than that in SC group (2/12foots)(T-test: P=0.000). 2. The time of eyeball diabrosis was 11~13days in AC group and 13--32+ days in VC group, and there wassignificant difference in this tWo groups (KaPlan(Meier survival analysis:P=0.000). 3. The intraocular melanomas could grow progressivelyoutside eyeball for a period, then it reduced and fell off All the micewere also alive. The size of the tumor on 32th days was 2.27I 1.97mmin AC grouP, 3.82f 1.85mm in VC grouP and 0.94 f2.27nun in SCgroupo There was significant difference of that betwCen VC and SCgrouP (P=0.003). 4. Tumor tissue necrosis on the center of thesubcutaneous melanomas could be observed in pathOlogical examination,but not in intraocular melanomas. Tumor metastasis could not be foundin the liver, spleen, and nodi lymPhatica.CONCLUSION. 1. Allogeneic tumor cells was exPressed progressivegrowth of intraocular tumors and transient growth of allogeneic tllmorsinjected suboutaneously. 2. The ways in which allogeneic tUmor cellsinduced immune privilege may be different betWeen AC and VC. 3.Allogenic intraocular melanomas in mice are good models in studingimmune privilege of eyes for its growth is similar to tha...