Immunopathogenesis of ovarian cancer.
Ovarian cancer, the most aggressive gynecologic cancer, is the foremost cause of death from gynecologic malignancies in the developed world. Over 90% of ovarian cancers arise from the surface epithelium, which are classified as epithelial ovarian cancer (EOC). EOCs can be categorized as serous, mucinous, endometrioid, clear cell, and transitional cell types. The molecular pathology of ovarian carcinomas is heterogeneous and involves various putative precursor lesions and multiple pathways of development. Furthermore, in another aspect, immune deficiencies that are present in the ovarian tumor environment enhance the progression of the tumor in the host. The presence of regulatory T cells, the inhibition of natural killer cytotoxic responses, the accumulation of myeloid suppressor cells in the tumor, deficiencies on interferon signaling, the secretion of cytokines that enhance tumor growth (i.e., IL-6, IL-10, CSF-1, TGF-b, TNF), and the expression of surface molecules (i.e., HLA-G, B7-H1, B7-H4, CD40, CD80) that have a role on immune suppression, are discussed in detail. The aim of this review is to provide insight of the evidence that supports the role of immunodeficiency in the progression of ovarian cancer and future directions for ovarian cancer therapies. It also discusses the genetic alterations in the subtypes of ovarian cancers.
Torres
M P
MP
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Ponnusamy
M P
MP
Lakshmanan
I
I
Batra
S K
SK
D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002277:Carcinoma / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000276:immunology; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D019013:CD40 Antigens; D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human