title: Sperm-associated antigens as targets for cancer immunotherapy: expression pattern and humoral immune response in cancer patients.
abstract: 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.
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia. karina@biomed.lu.lv
authors.forename: Karīna
authors.initials: K
authors.lastname: Siliņa
authors.forename: Pavel
authors.initials: P
authors.lastname: Zayakin
authors.forename: Zane
authors.initials: Z
authors.lastname: Kalniņa
authors.forename: Lāsma
authors.initials: L
authors.lastname: Ivanova
authors.forename: Irēna
authors.initials: I
authors.lastname: Meistere
authors.forename: Edgars
authors.initials: E
authors.lastname: Endzeliņš
authors.forename: Artūrs
authors.initials: A
authors.lastname: Abols
authors.forename: Aivars
authors.initials: A
authors.lastname: Stengrēvics
authors.forename: Mārcis
authors.initials: M
authors.lastname: Leja
authors.forename: Kristīne
authors.initials: K
authors.lastname: Ducena
authors.forename: Viktors
authors.initials: V
authors.lastname: Kozirovskis
authors.forename: Aija
authors.initials: A
authors.lastname: Linē
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D056724:Immunity, Humoral; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008868:Microtubule Proteins / Q000235:genetics / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D019496:Cancer Vaccines; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C450619:SPAG16 protein, human; C400106:SPAG6 protein, human; C099014:SPAG8 protein, human; D019204:GTP-Binding Proteins; C483942:SPAG1 protein, human