[Mechanism of immune escape in renal cell carcinoma].
OBJECTIVE
To investigate the mechanism of immune escape in renal cell carcinoma(RCC).


METHODS
Fas and FasL expressions were examined by immunohistochemical technique in 44 RCC patients, with the Ki67 expression and apoptosis of tumor infiltrating lymphocytes(TIL) monitored simultaneously. Cytokines including IL2 and IFN alpha were used to induce the expression of the renal carcinoma cell lines 786-0 cells. Combination treatment of 786-0 with cytokines and Anti-Fas monoclonal antibody (FasAb) was used to induce apoptosis. FasL function was assessed by in vitro co-culture assays using renal cancer cells 786-0 and Fas-sensitive Jurkat T-cells.


RESULTS
(1) Fas expression rate in RCC(22.8%) was lower than that in the controlled normal kidney tissues(53.8%, P < 0.01). FasL expression rate in RCC (46.5%) was higher than that in the controlled normal kidney tissues (23.2%, P < 0.01). That of Ki67 was 32.8%, with the expressions of Fas and Ki67 showing a negative correlation (r = -0.62, P < 0.05). In contrast, the expressions of FasL and Ki67 showed a positive correlation. (r = 0.93, P < 0.01). The Fas expression of stage I was significantly higher than that of stages III and IV. The expression rate of FasL in RCC was significantly increased with RCC stage (P < 0.01). (2) The apoptotic rate of TIL in RCC (33.9%) was significantly higher than that of the normal kidney tissues (3.5%, P < 0.01). The expression of FasL and the apoptotic rate of TIL in RCC gave a positive correlation (r = 0.96, P < 0.01). (3) Fas expression rate in 786-0 cells was 13.7%. The apoptotic rate mediated by FAsAb was 9.6%. IFN alpha was able to up-regulate the Fas expression and subsequently augment the FasAb-mediated apoptosis in 786-0 cells. But IL2 did not show similar effects. (4) The FasL expression rate of 786-0 was 18.6%. FasL expressed by 786-0 cells was able to induce apoptosis of Jurkat T-cells in co-culture assays and the apoptosis of Jurkat T-cells was significantly lowered after blocking the effect of FasL with Fas-neutralizing antibody NOK-2, giving the apoptotic rates of 14.9% and 2.0%, respectively, the difference therein is statistically significant (P < 0.01).


CONCLUSIONS
Down-regulation of Fas expression and up-regulation of FasL-expression are the mechanisms through which the RCC cells escape from immune attack.
Zheng
Junnian
J
Department of Urology, Xuzhou Medical College Hospital, Xuzhou 221002, China.
Sun
Xiaoqing
X
Chen
Jiacun
J
Jiang
Fujin
F
Li
Wang
W
Xie
Shuliang
S
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D007680:Kidney Neoplasms / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D019014:fas Receptor / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D019014:fas Receptor