Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patients

Usener, Dirk; Gerhardt, Axel; Schadendorf, Dirk; Eichmüller, Stefan B.

doi:10.1046/j.1365-2133.2003.05410.x

Cited by 15 publications

(14 citation statements)

References 37 publications

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“…So far all serologically defined antigens known for melanoma have been identified by SEREX [9], [12], and the SEREX database lists 102 melanoma-associated antigens (www2.licr.org/CancerImmunomeDB). Besides a number of unknown function and superfamily affiliations, and some cancer/testis antigen [1], [3], [5], [10], the vast majority of the SEREX-defined melanoma-associated antigens are of the same functional categories as those reported herein: chaperones, metabolic enzymes, proteins involved in protein biosynthesis and catabolism, structural proteins and regulators of the cellular metabolism. Galectin-3, found by SEREX and in the present study by proteome serology, is of great interest as it is one of the very few serologically defined tumor-associated antigens that are present at the outer cell surface.…”

Section: Discussionmentioning

confidence: 69%

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

et al. 2009

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Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2–6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins.

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Section: Discussionmentioning

confidence: 69%

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

et al. 2009

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“…Briefly, pre-absorbed sera from up to 16 CTCL patients and 14 healthy donors were used to determine the immunogenicity of the phage clones in at least two independent SEREX experiments. To identify GBP-5ta homologous genes, a cDNA library screening (HYREX) similar to the SEREX approach was performed as described previously (Usener et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

GBP-5 Splicing Variants: New Guanylate-Binding Proteins with Tumor-Associated Expression and Antigenicity

Fellenberg

Hartmann

Dummer

et al. 2004

Journal of Investigative Dermatology

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We have identified a new gene, gbp-5, with high homology to the guanylate binding proteins (GBP) belonging to the GTPase superfamily including the ras gene. gbp-5 is transcribed at least into three splicing variants (gbp-5a, -5b, and -5ta) leading to two different proteins (GBP-5a/b, GBP-5ta). GBP-5ta is C-terminally truncated by 97aa and has therefore lost its isoprenylation site. Although RT-PCR results indicated expression of GBP-5 members in selected normal tissues, western blotting using two newly generated antibodies revealed that expression of both proteins is restricted to peripheral blood monocytes with GBP-5ta at lower levels. In contrast, cutaneous T-cell lymphoma (CTCL) tumor tissues (seven of seven) were positive solely for GBP-5ta, and four of four CTCL cell lines expressed both proteins. Eight of nine melanoma cell lines expressed GBP-5a/b and four of nine additionally low levels of GBP-5ta. SEREX retesting using CTCL sera indicated a higher immunogenicity for GBP-5ta (nine of 16) than for GBP-5a/b (two of 11). Treatment of CTCL cell lines with interferon-gamma did not alter protein expression of GBP-5ta or GBP-5a/b. The restricted expression pattern of both GBP-5ta and GBP-5a/b and the pivotal role of many known members of the GTP-binding proteins in proliferation and differentiation suggest possible cancer-related functions of gbp-5.

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“…CT-antigens often cause spontaneous humoral responses in patients with cutaneous malignancies like melanoma (18,25) and cutaneous T-cell lymphoma (26). We used Western blotting and ELISA to investigate whether also NMSC patients display humoral immune responses to tumor antigens.…”

Section: No Spontaneous Humoral Immune Responses To Ct Antigens In Nmmentioning

confidence: 99%

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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Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patients

Abstract: Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes.

Cited by 15 publications

References 37 publications

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

GBP-5 Splicing Variants: New Guanylate-Binding Proteins with Tumor-Associated Expression and Antigenicity

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

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