GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction.

Abstract

Multiple mechanisms have been proposed to account for immune escape by tumors. Although gangliosides have long been known to suppress T-cell immunity, few studies have examined the effect of human tumor-derived gangliosides on immune responses. Here, we show that gangliosides isolated from renal cell carcinoma (RCC) cell lines and clear cell tumor tissue can induce apoptosis in peripheral blood T cells. The RCC tissue-derived gangliosides also suppressed IFN-gamma and, in many cases, interleukin-4 production by CD4+ T cells at concentrations (1 ng/mL-100 pg/mL) well below those that induce any detectable T-cell death (4-20 microg/mL). Additional findings show that GM2 expressed by RCC plays a significant role in promoting T-cell dysfunction. This is supported by the demonstration that all RCC cell lines examined (n = 5) expressed GM2 as did the majority of tumors (15 of 18) derived from patients with clear cell RCC. Furthermore, an antibody specific for GM2 (DMF10.167.4) partially blocked (50-60%) T-cell apoptosis induced by coculturing lymphocytes with RCC cell lines or with RCC tissue-derived gangliosides. DMF10.167.4 also partially blocked the suppression of IFN-gamma production induced by RCC tissue-derived gangliosides, suggesting that GM2 plays a role in down-regulating cytokine production by CD4+ T cells.

• Authors: Kaushik Biswas, Amy Richmond, Patricia Rayman, Soumika Biswas, Mark Thornton, Gaurisankar Sa, Tanya Das, Renliang Zhang, Ali Chahlavi, Charles S Tannenbaum, Andrew Novick, Ronald Bukowski, James H Finke
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 13 Pg. 6816-25 (Jul 01 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16818659 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• G(M2) Ganglioside

Topics

• Apoptosis (immunology)
• Carcinoma, Renal Cell (immunology, metabolism)
• Cell Line, Tumor
• Coculture Techniques
• G(M2) Ganglioside (biosynthesis, immunology)
• Humans
• Kidney Neoplasms (immunology, metabolism)
• T-Lymphocytes (immunology, pathology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)