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Spontaneous peripheral T-cell responses toward the tumor-associated antigen cyclin D1 in patients with clear cell renal cell carcinoma


Dannenmann, Stefanie R; Hermanns, Thomas; Bransi, Ali; Matter, Claudia; von Boehmer, Lotta; Stevanovic, Stefan; Schraml, Peter; Moch, Holger; Knuth, Alexander; van den Broek, Maries (2013). Spontaneous peripheral T-cell responses toward the tumor-associated antigen cyclin D1 in patients with clear cell renal cell carcinoma. Cancer Immunology Research, 1(5):288-295.

Abstract

Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2+ ccRCC for the presence of CD8+ T cells specific for TAA-derived HLA-A2–restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1–positive tumors. Cyclin D1–specific CD8+ T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8+ T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1–specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies

Abstract

Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2+ ccRCC for the presence of CD8+ T cells specific for TAA-derived HLA-A2–restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1–positive tumors. Cyclin D1–specific CD8+ T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8+ T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1–specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:15 Oct 2013 09:00
Last Modified:05 Apr 2016 17:03
Publisher:American Association for Cancer Research
ISSN:2326-6066
Publisher DOI:https://doi.org/10.1158/2326-6066.CIR-13-0113
PubMed ID:24777966

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