J Immunol. 2009 Oct 15;183(8):5050-8.

Elevated levels of select gangliosides in T cells from renal cell carcinoma patients is associated with T cell dysfunction.

Biswas S, Biswas K, Richmond A, Ko J, Ghosh S, Simmons M, Rayman P, Rini B, Gill I, Tannenbaum CS, Finke JH.

Source

Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation; Cleveland, OH 44195, USA.

Abstract

Increased expression of gangliosides by different tumor types including renal cell carcinoma (RCC) is thought to contribute to the immune suppression observed in cancer patients. In this study, we report an increase in apoptotic T cells from RCC patients compared with T cells from normal donors that coincided with the detection of T cells staining positive for GM2 and that the apoptosis was predominantly observed in the GM2(+) but not the GM2(-) T cell population. Ganglioside shedding from tumor rather than endogenous production accounts for GM2(+) T cells since there was no detectable level of mRNA for GM2 synthase in RCC patient T cells and in T cells from normal healthy donors after incubation with either purified GM2 or supernatant from RCC cell lines despite their staining positive for GM2. Moreover, reactive oxygen species as well as activated caspase 3, 8, and 9 were predominantly elevated in GM2(+) but not GM2(-) T cells. Similarly, increased staining for GD2 and GD3 but not GD1a was detected with patient T cells with elevated levels of apoptosis in the GD2(+) and GD3(+) cells. These findings suggest that GM2, GD2, and GD3 play a significant role in immune dysfunction observed in RCC patient T cells.

PMID:: 19801523; [PubMed - indexed for MEDLINE]
PMCID:: PMC2890308

Free PMC Article

Images from this publication.See all images (7) Free text

Figure 1

Ganglioside GM2 is detected on RCC patient T cells but not T cells isolated from normal donors. T cells were isolated from peripheral blood lymphocytes (PBLs) of patients and normal donors and subsequently stained for GM2 with mouse anti-human GM2 antibody (KM696). The relative expression of GM2 positive T cells was measured by flow cytometry (Fig. 1A & 1B). The percentage of GM2 positive T cells was determined by flow cytometric analysis of PBLs and TILs after staining cells with anti-CD3 and anti-GM2 antibody. As shown in Figure 1A, a significantly higher percentage of T cells (both localized and metastatic) stain positive for GM2 compared to normal donor T cells. Fig. 1B is a representative density plot showing that a higher percentage of T cells from the blood and tumor of RCC patients stain positive for GM2 as compared to normal PBLs. GM2+ T cells in both patient PBLs and TILs displayed significantly high Mean Fluorescence Intensity (MFI) as determined by flow cytometry (Figure 1C). Figure 1D is a representative histogram showing that both patient PBLs and TILs display high MFI by flow cytometry.

Elevated Levels of Select Gangliosides In T Cells From Renal Cell Carcinoma Patients Is Associated With T-Cell Dysfunction