Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specif... more Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specific serological biomarkers for the diagnosis of various solid cancers. Although the autoimmunity against thyroid tissue specific antigens has been studied extensively, so far, the autoantibody responses against common TAAs such as cancer-testis antigens (CTAs), mutated or differentiation antigens have not been comprehensively analyzed in patients with thyroid cancer. The current study aims to characterize the frequency of autoantibody responses against common TAAs in patients with thyroid cancer and benign thyroid nodules. A phage-displayed antigen microarray comprising 65 TAAs was produced and tested with sera from 53 patients with thyroid cancer, 90 patients with benign thyroid nodules and 96 cancer-free individuals, 100 melanoma, 54 breast cancer and 14 lung cancer patients as controls. A panel of 6 TAAs was identified that preferentially reacted with sera from patients with thyroid cancer. The top ranked antigen in this panel was GAGE1 eliciting autoantibody response in 6% of patients with thyroid cancer but not with benign nodules, whereas no reactivity to other CTAs was detected in the sera from patients with thyroid cancer. Although six TAAs, including one CTA, showed thyroid cancer-associated reactivity, overall, spontaneous humoral immune responses against TAAs are rare in thyroid cancer and their utility for the development of non-invasive assay for the differential diagnosis of thyroid nodules is limited.
The identification of novel cancer-related and immunogenic proteins is still a challenge to be fa... more The identification of novel cancer-related and immunogenic proteins is still a challenge to be faced to improve antigen-specific tumor immunotherapy. The category of so-called cancer-testis (CT) antigens is one of the most perspective groups of proteins for anticancer immune response activation as normally they are expressed in immunoprivileged tissues and are immunogenic if aberrantly generated in tumors. The heterogeneous group of proteins called sperm-associated antigens (SPAG) might encompass novel CT antigens owing to their common expression in male germ cells, their ability to elicit immune response underlying infertility, and lately proposed oncogenic properties. We carried out a comprehensive analysis of the expression pattern in various normal and cancerous tissues and assessed the frequency of spontaneous humoral immune response against members of the SPAG group in cancer patients using phage-displayed antigen microarrays. Our results show that out of 15 analyzed SPAG genes only SPAG1, SPAG6, SPAG8, SPAG15, and SPAG17 are predominantly expressed in testis, whereas the others are ubiquitously expressed with only a testis-associated alternative splice variant of SPAG16. mRNA expression of SPAG1, SPAG6, and alternative splice variants of SPAG8, SPAG16, and SPAG17 was elevated in various tumors with frequencies ranging from approximately 10% to 70%. The upregulation of SPAG6 in lung and breast cancer was confirmed by immunohistochemical analysis of tumor and normal tissue microarrays. Cancer-associated spontaneous humoral immune response was detected against SPAG1, SPAG6, SPAG8, and a novel testis-specific splice variant of SPAG17 and ascribe these as novel CT antigens that potentially are applicable as immunotherapeutic targets and serologic biomarkers.
Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specif... more Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specific serological biomarkers for the diagnosis of various solid cancers. Although the autoimmunity against thyroid tissue specific antigens has been studied extensively, so far, the autoantibody responses against common TAAs such as cancer-testis antigens (CTAs), mutated or differentiation antigens have not been comprehensively analyzed in patients with thyroid cancer. The current study aims to characterize the frequency of autoantibody responses against common TAAs in patients with thyroid cancer and benign thyroid nodules. A phage-displayed antigen microarray comprising 65 TAAs was produced and tested with sera from 53 patients with thyroid cancer, 90 patients with benign thyroid nodules and 96 cancer-free individuals, 100 melanoma, 54 breast cancer and 14 lung cancer patients as controls. A panel of 6 TAAs was identified that preferentially reacted with sera from patients with thyroid cancer. The top ranked antigen in this panel was GAGE1 eliciting autoantibody response in 6% of patients with thyroid cancer but not with benign nodules, whereas no reactivity to other CTAs was detected in the sera from patients with thyroid cancer. Although six TAAs, including one CTA, showed thyroid cancer-associated reactivity, overall, spontaneous humoral immune responses against TAAs are rare in thyroid cancer and their utility for the development of non-invasive assay for the differential diagnosis of thyroid nodules is limited.
The identification of novel cancer-related and immunogenic proteins is still a challenge to be fa... more The identification of novel cancer-related and immunogenic proteins is still a challenge to be faced to improve antigen-specific tumor immunotherapy. The category of so-called cancer-testis (CT) antigens is one of the most perspective groups of proteins for anticancer immune response activation as normally they are expressed in immunoprivileged tissues and are immunogenic if aberrantly generated in tumors. The heterogeneous group of proteins called sperm-associated antigens (SPAG) might encompass novel CT antigens owing to their common expression in male germ cells, their ability to elicit immune response underlying infertility, and lately proposed oncogenic properties. We carried out a comprehensive analysis of the expression pattern in various normal and cancerous tissues and assessed the frequency of spontaneous humoral immune response against members of the SPAG group in cancer patients using phage-displayed antigen microarrays. Our results show that out of 15 analyzed SPAG genes only SPAG1, SPAG6, SPAG8, SPAG15, and SPAG17 are predominantly expressed in testis, whereas the others are ubiquitously expressed with only a testis-associated alternative splice variant of SPAG16. mRNA expression of SPAG1, SPAG6, and alternative splice variants of SPAG8, SPAG16, and SPAG17 was elevated in various tumors with frequencies ranging from approximately 10% to 70%. The upregulation of SPAG6 in lung and breast cancer was confirmed by immunohistochemical analysis of tumor and normal tissue microarrays. Cancer-associated spontaneous humoral immune response was detected against SPAG1, SPAG6, SPAG8, and a novel testis-specific splice variant of SPAG17 and ascribe these as novel CT antigens that potentially are applicable as immunotherapeutic targets and serologic biomarkers.
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Papers by Pawel Zayakin