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

Abstract

Similarities between the pathologic progression of cancer and the physiologic process of placentation (e.g., 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, prostrate, endometrial and ovarian cancer, but their involvement as putative mediators of the immunologic escape of cancer are 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 key words: 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 anti-tumor immunity and improve survival.

Conjunctival Melanoma during Pregnancy

“…Sex hormones have been shown to play a role in the growth of some tumours such as breast, prostate, endometrial, and ovarian [16]. It has been reported that conjunctival melanocytic lesions express hormone receptors (progesterone and oestrogen), which might explain why these tumours may grow during pregnancy and alter their appearance and behave differently under hormonal changes [17], akin to their cutaneous counterparts [18,19].…”

Current position of TNF-α in melanomagenesis

“…A paradigm in the melanoma development has recently emerged, the parallel between pregnancy and cancer [4,11]. Similarities between the mechanisms involved in the maternal-fetus tolerance and the tumor escape from the host's immune cells have been found.…”

Progesterone and Melanoma Cells: An Old Story Suspended between Life and Death

“…Others larger multivariate analyses, however, demonstrated that it was equally strong in pre-as well as in post-menopausal groups [20]. Parallely, the literature concerning melanoma progression in pregnancy is also controversial [21][22][23][24], although several recent reports demonstrate that pregnancyassociated melanomas have poorer outcomes than other melanomas [25][26][27][28][29].…”

“…Others larger multivariate analyses, however, demonstrated that it was equally strong in pre-as well as in post-menopausal groups [20]. Parallely, the literature concerning melanoma progression in pregnancy is also controversial [21][22][23][24], although several recent reports demonstrate that pregnancyassociated melanomas have poorer outcomes than other melanomas [25][26][27][28][29].In vitro progesterone influences melanoma growth [30][31][32][33], but several melanoma cell lines have been studied and very different experimental protocols have been used, so that the results actually available in literature are not univocal. Further research on this topic is thus needed, especially in view of the widespread use of PG in clinical practice.…”