Effect of Dietary Selenium and Cancer Cell Xenograft on Peripheral T and B Lymphocytes in Adult Nude Mice

Abstract

Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8(+) and CD4(+) T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na(2)SeO(4)) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10(6) cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se - or Se++ diet and the CD4(+) T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4(+) or CD8(+) T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25(+)CD4(+) T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4(+), but not CD8(+) T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.

Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals

“…However, extrathymic maturation (spleen, lymph node, and bone marrow) of T cells (NK cells) could be possible when these mice have been burdened with virus or tumor, as reported by several other investigators. 44, 45 Cheng et al 46 also report that selenium increased peripheral and spleen CD4 + and CD8 + cells in the nude mice bearing prostate cancer cells. Moreover, it is noteworthy that postnatal thymic-independent T cell differentiation (maturation) in the extrathymic origin (such as in skin) could be possible.…”

Selenium and selenoproteins in prostanoid metabolism and immunity

“…Several reports have suggested that Se levels might regulate the function of B cells. Mice fed Se-deficient (0 mg/kg) or Se-high (1.0 mg/kg) diets showed decreased numbers of peripheral B cells (Cheng et al 2012). Similar trends were seen in SeMet-treated mice where mice on low (0.02 ppm) and above-adequate (2 ppm) diets had reduced B cell numbers in the spleen (Vega et al 2007).…”

“…T cells from mice fed high Se diet (1.0 mg/kg) had a much higher proliferation rate than those from Se low (0.08 mg/kg) and medium (0.25 mg/kg) diets (Hoffmann FW et al 2010). An in vivo study using athymic, immune-deficient NU/J nude mice showed that CD4 + T cells were increased in Se-sufficient mice (1.0 mg/kg) compared to mice on Se-deficient (0 mg/kg) or Se-adequate (0.15 mg/kg) diets (Cheng et al 2012). Furthermore, higher Se levels increased free thiols in activated CD4 + T cells, which likely played an important role in the clonal expansion of these cells by favoring the TCR-induced oxidative burst in cells (Hoffmann FW et al 2010).…”

A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy

“…Interestingly, we also found that compared to high-dose CN133 (5 mg/kg), CN133 with low dose (1 mg/kg) conferred to a marked reduction in tumors volume in xenograft prostate cancer model of nude mice in our previous study [ 38 ]. Although nude mice are useful model to assess tumor xenograft development because of athymic congenitally, extrathymic T cells including CD4 + or CD8 + cells could partially develop maturation as age growth in nude mice [ 41 , 42 ]. Therefore, data from this time and our previous results demonstrated that low-dose CN133 may efficaciously suppress prostate cancer growth by augment of immunogenicity.…”