Tumor-specific CTL kill murine renal cancer cells using both perforin and Fas ligand-mediated lysis in vitro, but cause tumor regression in vivo in the absence of perforin.

摘要: Kidney cancer is a devastating disease; however, biological therapies have achieved some limited success. The murine renal Renca has been used as model for developing new preclinical approaches to the treatment of cell carcinoma. Successful cytokine-based require CD8(+) T cells, but exact mechanisms by which cells mediate therapeutic benefit not completely identified. After successful therapy in BALB/c mice, we generated CTLs vitro using mixed lymphocyte tumor cultures. These CTL mediated tumor-specific H-2K(d)-restricted lysis and production IFN-gamma, TNF-alpha, Fas ligand (FasL) response Renca. both granule- FasL-mediated lyse Renca, although granule-mediated killing was predominant lytic mechanism vitro. cytokines IFN-gamma TNF-alpha increased sensitivity death pathways. Adoptive transfer these anti-Renca into tumor-bearing mice cured most established experimental pulmonary metastases, successfully treated were immune rechallenge. Interestingly, able establish Renca-specific from gene targeted perforin (pfp(-/-)) mice. Although pfp(-/-) showed reduced cytotoxic activity against their presence targets equivalent that wild-type CTL, adoptive efficient causing regression metastases. Therefore, paramount importance CTL-mediated vitro, major vivo effector clearly are independent perforin.