Cancer/Testis Antigens: Expression, Regulation, Tumor Invasion, and Use in Immunotherapy of Cancers.
Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy. Evolving evidence reveals that a number of CTAs stimulate epithelial mesenchymal transition (EMT) and generation of cancer stem-like cells, intensifying metastasis, invasion, and tumorigenesis. Based on these features, CTAs attract attention to be considered as ideal targets for developing several clinical trials, many of them concentrating on CTA vaccine therapy. According to recent practical clinical interest, more characterizations of CTA regulation are identified. CTA expression has been demonstrated in a variety of human cancer tissues, and some of them have been found to elicit humoral and/or cellular immune responses in cancer patients. CTAs are brilliant targets for anticancer drug discovery, targeted tumor therapy, and diagnostic biomarkers, furthermore, valued genes in the study of immunotherapy, promoting tumorigenesis, and malignant progression. This review outlines and categorizes our current understanding of the complex and biased process of CTAs mRNA and protein expression in cancer, and supplies the most recent information on their regulation and function. Besides, a concise synopsis of the major clinical trials involving CTAs, as therapeutic avenues, is discussed.


BACKGROUND
AIRE: autoimmune regulator; cAMP: cyclic adenosine 3',5'-cyclic monophosphate; CEA: carcinoembryonic antigen; CML: chronic myeloid leukemia; CREB: cyclicamp response element binding; CSCs: cancer stem cells; CTAs: cancer/testis antigens; CTL: cytotoxic T lymphocyte; DCs: dendritic cells; EMT: epithelial-mesenchymal transition; ERK: extracellular signal-regulated kinase; ESCC: esophageal squamous cell carcinoma; ETS: E26 transformation-specific; His: histidine; HLA: human leukocyte antigen; HNSCC: head and neck squamous cell carcinoma; IFN-γ: interferon-γ; IHC: Immunohistochemistry; IL-7: Interleukin7; MHC: major histocompatibility complex; MMP2: matrix metalloproteinase 2; mTECs: medullary thymus epithelial cells; MUC1: mucin 1; NSCLC: non-small cell lung cancer; PRAME: preferentially expressed antigen in melanoma; RDA: representational difference analysis; SEREX: serological analysis of cDNA expression; SSX: synovial sarcoma X chromosome; TAAs: tumor-associated antigens; TCR: T-cell receptor; TCGA: The Cancer Genome Atlas; TGF-β: transforming growth factor-β.
a Student Research Committee, Medical Genetics Research Center , Mashhad University of Medical Sciences , Mashhad , Iran.|b Cancer Immunology Project (CIP) , Universal Scientific Education and Research Network (USERN) , Mashhad , Iran.
Arash
A
Salmaninejad
c Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|d Network of Immunity in Infection, Autoimmunity and Malignancy (NIIMA) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran.
Mohammad Reza
MR
Zamani
e Department of Biology , Faculty of Sciences, University of Guilan , Rasht , Iran.
Mehrnaz
M
Pourvahedi
f Department of Medical Genetics, School of Medicine , Tehran University of Medical Sciences , Tehran Iran.
Zahra
Z
Golchehre
f Department of Medical Genetics, School of Medicine , Tehran University of Medical Sciences , Tehran Iran.
Ali
A
Hosseini Bereshneh
c Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|d Network of Immunity in Infection, Autoimmunity and Malignancy (NIIMA) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran.|g Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
Nima
N
Rezaei
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology*; D063646:Carcinogenesis; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008297:Male; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D013737:Testis / Q000378:metabolism*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines
Cancer; cancer/testis antigens; expression; immunotherapy; regulation