The Biology of Mantle Cell Lymphoma: Exploring the Gender Difference in Mantle Cell Lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare B cell neoplasm that accounts for approximately 4-8% of non-Hodgkin’s lymphomas (NHLs). The median age at diagnosis is 65 years with a male to female predominance of 3:1. It has also been demonstrated that female MCL patients have a greater response to therapy, especially immunomodulatory therapy compared to male MCL patients. The concept of cancer immunosurveillance is well described and it is perceived that females mount a greater immune response compared to males. In addition, although lymphomas are generally not perceived to be hormone controlled, epidemiological studies have demonstrated lower prevalence of lymphoma in females taking exogenous oestrogen. This aim of this thesis was to explore the gender difference observed in MCL. The study investigated the difference in the quantity of immune cells in the peripheral blood and lymph node biopsies of untreated male and female MCL patients. There was a significantly greater number of T cells in the peripheral blood of male MCL patients compared to the female MCL patients. Conversely, greater numbers of immune cells were observed in the lymph node biopsies of female MCL patients compared to male MCL patients. In addition, four NK cell activating receptors; NKp46, NKp44, NKp30 and NKG2D were examined to determine if their expression was different between the genders.

The cell mediated cytotoxic function of the immune cells (PBMCs) from male and female MCL patients and healthy controls was also examined. Interestingly the healthy controls exhibited greater cytotoxicity compared to the MCL patients. PBMCs were incubated with oestrone (female hormone in postmenopausal women), lenalidomide and IL-2 to further investigate the effects of these on the immune cells from male and female MCL patients. Incubation with IL-2 resulted in a significant increase in the cytotoxicity activity of male MCL patients but not female MCL patients in this cohort.

The lymph node biopsies from MCL patients were examined for the presence of oestrogen receptors. Oestrogen receptor β was predominantly expressed on MCL cells in all the biopsies examined. This is an area that warrants further studies. This thesis provides some insight into the mechanisms that may influence the gender difference observed in MCL, however further studies are needed.