Previous reports from our laboratories and others suggested a role for tumor-derived gangliosides in tumor-induced immune dysfunction, a process that may impair the development of an effective immune response to renal cell carcinoma (RCC), the most predominant form of kidney cancer. Though there has been some isolated reports relating GM2 to tumor progression and metastasis, evidence suggesting a role for GM2 in mediating immune dysfunction in cancer patients is lacking. In this study we report a novel apoptotic function of RCC derived GM2 in mediating immune dysfunction in RCC patients. HPLC data is presented showing that GM2 expression is significantly increased in clear cell RCC tissue compared to normal adjacent tissue (9/16). The mass of GM2 was confirmed in gangliosides isolated from RCC tumors by mass spectrometry analyses (LC/ESI/MS/MS). Immunostaining with anti-GM2 antibody also revealed increased expression of GM2 in freshly cultured tumor cells versus adjacent normal cells. Real time PCR demonstrated increased expression of GM2 synthase mRNA in tumor over normal tissue. Gangliosides isolated from RCC tissue and RCC cell lines induced apoptosis of T cells as did co-culturing with RCC lines expressing GM2. Apoptosis of T cells was assessed by the TUNEL assay after 48 hours of incubation with gangliosides or tumor cells. Further, apoptosis of T cells induced by RCC derived gangliosides and RCC cell lines was blocked significantly with anti-GM2 antibody suggesting the potential role of GM2 in tumor induced immune dysfunction in RCC.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]