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Review
. 2014 Apr;89(4):520-35.
doi: 10.1016/j.mayocp.2014.01.006.

Immunomodulatory effects of sex hormones: requirements for pregnancy and relevance in melanoma

Elizabeth Ann L Enninga  1 , Shernan G Holtan  2 , Douglas J Creedon  3 , Roxana S Dronca  4 , Wendy K Nevala  4 , Simona Ognjanovic  1 , Svetomir N Markovic  5
Affiliations
Review

Immunomodulatory effects of sex hormones: requirements for pregnancy and relevance in melanoma

Elizabeth Ann L Enninga et al. Mayo Clin Proc. 2014 Apr.

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.

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Conflict of interest statement

Conflict of Interest Statement: No conflicts of interest to disclose

Figures

Figure 1
Figure 1
Hormonal changes in week of hormones important for the regulation of gestation in healthy pregnant women. CRH = corticotropin releasing hormone; hCG = human chorionic gonadotropin.
Figure 2
Figure 2
Effects of sex hormones during early pregnancy to promote implantation and fetal tolerance and the proposed role in initiation of cancer. CRH = corticotropin releasing hormone; E2 = estradiol; hCG = human chorionic gonadotropin; IFN = interferon; IL = interleukin; uNK = uterine natural killer cell; VEGFR = vascular endothelial growth factor receptor.
Figure 3
Figure 3
Maintenance and regulation of tolerance by sex hormones during mid-pregnancy and the proposed role of hormones in progression/metastasis of cancer. CRH = corticotropin releasing hormone; C3 = complement component 3; ER = estrogen receptor; E2 = estradiol; E3 = estrone; hCG = human chorionic gonadotropin; IFN= interferon; IL = interleukin; PlBF = placental binding factor; TNF = tumor necrosis factor; VEGF = vascular endothelial growth factor.
Figure 4
Figure 4
Role of sex hormones in the promotion of inflammation and labor as a natural method for provoking regression of tumor in cancer patients. bFGF = basic fibroblast growth factor; CRH = corticotropin releasing hormone; CRHBP = corticotropin releasing hormone binding protein; E2 = estradiol; hCG = human chorionic gonadotropin; hPRL = human prolactin; IFN = interferon; IL= interleukin; PR = progesterone receptor; VEGF= vascular endothelial growth factor.
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Comment in

References

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