TGF-alpha as a candidate tumor antigen for renal cell carcinomas.
OBJECTIVE
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)-alpha, leading us to hypothesize that TGF-alpha could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study.


RESULTS
We first confirmed the absent or weak expression of TGF-alpha 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-alpha, by expanding many T cell lines specific for certain TGF-alpha peptides or the mature TGF-alpha protein, when presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-alpha-specific T cells were polyfunctionals and secreted IFN-gamma, TNF-alpha and IL-2.


CONCLUSIONS
We have shown that TGF-alpha is a valid candidate TAA, which should allow the development of a targeted immunotherapy.
Pelletier
Sandy
S
Department of Medicine, CRCHUM-Hôpital Notre-Dame, Université de Montréal, Montreal, Canada.
Tanguay
Simon
S
Lee
Stephen
S
Gunaratnam
Lakshman
L
Arbour
Nathalie
N
Lapointe
Réjean
R
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000276:immunology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D010455:Peptides; D016211:Transforming Growth Factor alpha; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human