The role of mast cells and their mediators in reproduction, pregnancy and labour

BACKGROUND: Mast cells (MCs) are the classical mediators of allergy, however, their importance in the development of innate and adaptive immune responses is increasingly being recognized. Herein, the present MC literature is summarized, with particular focus on studies of MCs in the endometrium and myometrium, and their involvement in fertility, implantation, pregnancy and labour. METHODS: Recent developments in MC biology were identified by systematic searches of PubMed, Medline and Google Scholar from 2000 to November 2009. To specifically examine the role of MCs in fertility and pregnancy, we then performed a systematic review of English literature cited in the PubMed, Medline and Google Scholar databases, but extended the search period, from 1980 to January 2010 RESULTS: MCs can respond to immunoglobulin E-independent innate immune stimuli and are present within the endometrium, with activation and release of mediators occurring prior to menstruation and in association with endometriosis. With respect to pregnancy, MCs are redundant during blastocyst implantation and although their mediators can induce myometrial contractility, there is no epidemiological link of preterm birth with allergy, suggesting a non-essential role or robust regulation. In males, MCs are present in the testes and are increased in oligo- and azoospermia, with MC mediators directly suppressing sperm motility in a potentially reversible manner. CONCLUSIONS: MCs are prevalent in the female and male reproductive tract. However, whether MCs are absolutely required for a successful pregnancy or are fundamental to reproductive pathology, and thereby a therapeutic target, remains to be determined

Suppression, subversion and escape: the role of regulatory T cells in cancer progression

Regulatory T cells (T<sub>regs</sub>) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. However, in the context of cancer their role is more complex, and they are thought to contribute to the progress of many tumours. As cancer cells express both self- and tumour-associated antigens, T<sub>regs</sub> are key to dampening effector cell responses, and therefore represent one of the main obstacles to effective anti-tumour responses. Suppression mechanisms employed by T<sub>regs</sub> are thought to contribute significantly to the failure of current therapies that rely on induction or potentiation of anti-tumour responses. This review will focus on the current evidence supporting the central role of T<sub>regs</sub> in establishing tumour-specific tolerance and promoting cancer escape. We outline the mechanisms underlying their suppressive function and discuss the potential routes of T<sub>regs</sub> accumulation within the tumour, including enhanced recruitment, in-situ or local proliferation, and de-novo differentiation. In addition, we review some of the cancer treatment strategies that act, at least in part, to eliminate or interfere with the function of T<sub>regs</sub>. The role of T<sub>regs</sub> is being recognized increasingly in cancer, and controlling the function of these suppressive cells in the tumour microenvironment without compromising peripheral tolerance represents a significant challenge for cancer therapies

Clinical value of immunohistochemically detected lymphatic and vascular invasions in clinically staged endometrioid endometrial cancer

<p>Background: A novel technique to differentiate lymphatic from vascular invasion and to assess the clinicopathological significance in patients with early endometrial cancer.</p> <p>Methods: Dual immunohistochemical techniques against pancytokeratin epithelial cell marker (PCK), D6 lymphatic endothelial marker, and CD31 nonspecific endothelial marker were deployed for differentiation. Seventy-seven patients were included with a median follow-up of 161 months. Tumors with positive evidence of lymphovascular space invasion on PCK-CD31 immunohistochemistry and absence of lymphatic space invasion on PCK-D6 were regarded as cases with vascular space invasion only.</p> <p>Results: Significant association between depth of myometrial invasion, recurrence rate, and hematoxylin and eosin that detected lymphovascular space invasion were noted (P < 0.0001 and P = 0.009, respectively). The 5-year recurrence-free survival was 45% for the group with hematoxylin and eosin evidence of lymphovascular space invasion compared with 89% for the group without (P = 0.0014). Pancytokeratin epithelial cell marker-D6 dual immunostaining detected lymphatic space invasion in 22 (29%) patients. There was significant association between lymphatic space invasion and depth of myometrial invasion (P = 0.046). Lymphatic space invasion detected on immunohistochemistry was present in 8 (72%) of 11 patients with recurrent disease. Of the remaining 49 patients with no evidence of recurrent disease, only 11 (22%) had presented with lymphatic space invasion. Positive association between tumor recurrence rate and lymphatic space invasion was noted (P = 0.003). The 5-year recurrence-free survival was 53% for the group with lymphatic invasion compared with 93% for the group without. This difference was similarly shown to be of significance (P = 0.0009). There were no apparent association between immunohistochemically detected lymphovascular or vascular space invasion and any clinicopathological factor.</p> <p>Conclusions: Lymphatic space invasion detected by using dual immunostaining is of significant value in identifying high-risk patients.</p&gt

Reply to: “Experimental aspects of copy number variant assays at CCL3L1”

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