Immunomodulatory Effects of Sex Hormones: Requirements for Pregnancy and Relevance in Melanoma

• Published in: Mayo Clinic proceedings Vol. 89; no. 4; pp. 520 - 535
• Main Authors: Enninga, Elizabeth Ann L., BS, Holtan, Shernan G., MD, Creedon, Douglas J., MD, PhD, Dronca, Roxana S., MD, Nevala, Wendy K., MS, Ognjanovic, Simona, PhD, Markovic, Svetomir N., MD, PhD
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.04.2014; Elsevier, Inc; Elsevier Limited
• Subjects: Adult; Analysis; Chorionic gonadotropin; Chorionic Gonadotropin - immunology; Chorionic Gonadotropin - metabolism; Chorionic Gonadotropin - therapeutic use; Development and progression; Estrogens - immunology; Estrogens - metabolism; Estrogens - therapeutic use; Female; Gestational Age; Gonadal Steroid Hormones - immunology; Gonadal Steroid Hormones - metabolism; Gonadal Steroid Hormones - therapeutic use; Health aspects; Hormones, Sex; Humans; Immune System Phenomena - immunology; Immune System Phenomena - physiology; Immunologic Factors; Immunomodulation - immunology; Immunomodulation - physiology; Internal Medicine; Melanoma; Melanoma - drug therapy; Melanoma - immunology; Melanoma - pathology; Pregnancy; Pregnancy Complications, Neoplastic - drug therapy; Pregnancy Complications, Neoplastic - immunology; Pregnancy Complications, Neoplastic - pathology; Pregnant women; Progesterone - immunology; Progesterone - metabolism; Progesterone - therapeutic use; Prognosis; Risk factors; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Treatment Outcome; estradiol-17β; PR; nuclear factor kappa B; uterine natural killer; PRL; E2; hCG; progesterone receptor; human chronic gonadotropin; NF-κB; IFN-γ; natural killer; tumor necrosis factor alpha; overall survival; CTLA4; PlGF; hypothalamic-pituitary-adrenal; corticotropin-releasing hormone; interferon gamma; prolactin; OS; regulatory T; estrogen receptor; VEGF; Treg; ER; placental growth factor; uNK; TNF-α; vascular endothelial growth factor; cytotoxic T lymphocyte antigen 4; CRH; HPA; program death 1; NK; PD-1; dendritic cell; DC
• ISSN: 0025-6196; 1942-5546
• DOI: 10.1016/j.mayocp.2014.01.006

Abstract Similarities between the pathologic progression of cancer and the physiologic process of placentation (eg, proliferation, invasion, and local/systemic tolerance) have been recognized for many years. Sex hormones such as human chorionic gonadotropin, estrogens, progesterone, and others contribute to induction of immunologic tolerance at the beginning of gestation. Sex hormones have been shown to play contributory roles in the growth of cancers such as breast cancer, prostrate cancer, endometrial cancer, and ovarian cancer, but their involvement as putative mediators of the immunologic escape of cancer is still being elucidated. Herein, we compare the emerging mechanism by which sex hormones modulate systemic immunity in pregnancy and their potentially similar role in cancer. To do this, we conducted a PubMed search using combinations of the following keywords: “immune regulation,” “sex hormones,” “pregnancy,” “melanoma,” and “cancer.” We did not limit our search to specific publication dates. Mimicking the maternal immune response to pregnancy, especially in late gestation, might aid in design of better therapies to reconstitute endogenous antitumor immunity and improve survival.