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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1207-1218 |
| Number of pages | 12 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 58 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2009 |
| Externally published | Yes |
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Keywords
- Cancer immunotherapy
- Clear cell renal cell carcinoma
- Polyfunctional antigen-specific T lymphocytes
- Transforming growth factor (TGF)-α
- Tumor antigen
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Immunology
- Immunology and Allergy
Cite this
TGF-alpha as a candidate tumor antigen for renal cell carcinomas. / Pelletier, Sandy; Tanguay, Simon; Lee, Stephen; Gunaratnam, Lakshman; Arbour, Nathalie; Lapointe, Réjean.
In: Cancer Immunology, Immunotherapy, Vol. 58, No. 8, 08.2009, p. 1207-1218.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TGF-alpha as a candidate tumor antigen for renal cell carcinomas
AU - Pelletier, Sandy
AU - Tanguay, Simon
AU - Lee, Stephen
AU - Gunaratnam, Lakshman
AU - Arbour, Nathalie
AU - Lapointe, Réjean
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Cancer immunotherapy
KW - Clear cell renal cell carcinoma
KW - Polyfunctional antigen-specific T lymphocytes
KW - Transforming growth factor (TGF)-α
KW - Tumor antigen
UR - http://www.scopus.com/inward/record.url?scp=67349208136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349208136&partnerID=8YFLogxK
U2 - 10.1007/s00262-008-0630-2
DO - 10.1007/s00262-008-0630-2
M3 - Article
C2 - 19052740
AN - SCOPUS:67349208136
VL - 58
SP - 1207
EP - 1218
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 8
ER -