Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma

Atanackovic, Djordje; I, Blum; Cao, Yanran; Wenzel, Stefan; Bartels, Katrin; Faltz, Christiane; Hossfeld, Dieter K.; Hegewisch‐Becker, Susanna; Bokemeyer, Carsten; Leuwer, R.

doi:10.4161/cbt.5.9.3174

Cited by 63 publications

(83 citation statements)

References 22 publications

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“…CT-antigens are frequently coexpressed in various malignancies (20)(21)(22). Our results in NMSC confirmed these observations, as more than 40% of NMSC biopsies coexpressed ≥2 antigens and we observed examples of coexpression of as much as 11 antigens (Fig.…”

Section: Ct-antigens Are Broadly Expressed In Nmscsupporting

confidence: 78%

Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas

Walter

Barysch

Behnke

et al. 2010

Clinical Cancer Research

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Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.Experimental Design: We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western blotting and ELISA. MHC-I expression and CD8 + T-cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimodtreated BCC patients.Results: We found expression of at least one CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen-specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8 + cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8 + T cells.

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Section: Ct-antigens Are Broadly Expressed In Nmscsupporting

confidence: 78%

Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas

Walter

Barysch

Behnke

et al. 2010

Clinical Cancer Research

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“…First, we selected 20 CT genes characterized by a strictly testis-specific expression and absence from any other healthy tissues as demonstrated in our previous studies [17][18][19]. The expression of these genes was then analyzed in 10 untreated AML cell lines by RT-PCR.…”

Section: Aml Cell Lines Show a Scarce Constitutive Expression Of Ctamentioning

confidence: 99%

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

et al. 2011

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Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N 5 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5 0 -aza-2 0 -deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2. Am. J. Hematol. 86:918-922, 2011. V

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“…A subset of the CT genes has been shown to encode antigens that are immunogenic and elicit humoral and cellular immune responses in cancer patients (2). Because of their restricted expression profile in normal tissues and because the testis is an immunoprivileged site, the CT antigens are emerging as strong candidates for therapeutic cancer vaccines, as revealed by early-phase clinical trials (3)(4)(5)(6)(7)(8)(9)(10). Biologically, the CT genes provide a model to better understand complex gene regulation and aberrant gene activation during cancer.…”

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confidence: 99%

Genome-wide analysis of cancer/testis gene expression

Hofmann

Caballero

Stevenson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

300

309

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Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genomewide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted (39), testis/brain-restricted (14), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testisrestricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets.gene index ͉ prediction

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Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma

Cited by 63 publications

References 22 publications

Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas

Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas

Cancer‐testis antigen expression and its epigenetic modulation in acute myeloid leukemia

Genome-wide analysis of cancer/testis gene expression

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