TGF-alpha as a candidate tumor antigen for renal cell carcinomas |
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Authors: | Sandy Pelletier Simon Tanguay Stephen Lee Lakshman Gunaratnam Nathalie Arbour Réjean Lapointe |
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Affiliation: | 1.Department of Medicine,CRCHUM-H?pital Notre-Dame, Université de Montréal,Montreal,Canada;2.Institut du Cancer de Montreal,Montreal,Canada;3.McGill University Health Centre, Montreal General Hospital,Montreal,Canada;4.Department of Cellular and Molecular Medicine, Faculty of Medicine,University of Ottawa,Ottawa,Canada;5.Centre de Recherche,CRCHUM-H?pital Notre-Dame,Montreal,Canada |
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Abstract: | Objectives Patients with renal cell carcinomas (RCC) have few treatment options, underscoring the importance of developing new approaches such as immunotherapy. However, few tumor associated antigens (TAA), which can be targeted by immunotherapy, have been identified for this type of cancer. von Hippel-Lindau clear cell RCC (VHL−/−RCC) are characterized by mutations in the VHL tumor suppressor gene. Loss of VHL function causes the overexpression of transforming growth factor (TGF)-α, leading us to hypothesize that TGF-α could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study. Methods and results We first confirmed the absent or weak expression of TGF-α in important normal tissues as well as its overexpression in 61% of renal tumors in comparison to autologous normal kidney tissues. In addition, we demonstrated the immunogenicity of TGF-α, by expanding many T cell lines specific for certain TGF-α peptides or the mature TGF-α protein, when presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-α-specific T cells were polyfunctionals and secreted IFN-γ, TNF-α and IL-2. Conclusion We have shown that TGF-α is a valid candidate TAA, which should allow the development of a targeted immunotherapy. |
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Keywords: | Transforming growth factor (TGF)-α Clear cell renal cell carcinoma Tumor antigen Cancer immunotherapy Polyfunctional antigen-specific T lymphocytes |
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