The Effects of Tamoxifen on Immunity

Behjati, Sam; Frank, Markus H.

doi:10.2174/092986709788803042

Cited by 104 publications

(100 citation statements)

References 29 publications

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“…ERβ ligands have been proposed as the next-generation estriol treatment, given their protective effect across both sexes [42]. It should be noted that the immunomodulatory effects of tamoxifen may be independent of the estrogen-receptor with its immunomodulation mediated through the multidrug resistance gene product, permeability-glycoprotein [43].…”

Section: Estradiol Synthetic Estrogens and Estriolmentioning

confidence: 99%

The Role of Sex Hormones in Multiple Sclerosis

et al. 2018

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Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder with an immune-mediated pathophysiology that affects the central nervous system (CNS). Like other autoimmune conditions, it has a predilection for female gender. This suggests a gender bias and a possible hormonal association. Inflammation and demyelination are hallmarks of MS. Oligodendrocytes are the myelinating cells of the CNS and these continue to be generated by oligodendrocyte precursor cells (OPCs). The process of remyelination represents a major form of plasticity in the developing adult CNS. Remyelination does occur in MS, but the process is largely inadequate and/or incomplete. Current treatment strategies primarily focus on reducing inflammation or immunosuppression, but there is a need for more extensive research on re-myelination as a possible mechanism of treatment. Previous studies have shown that pregnancy leads to an increase in OPC proliferation, oligodendrocyte generation and the number of myelinated axons in the maternal CNS. Studies have also suggested that this remyelination is possibly mediated by estriol. Sex hormones in particular have been shown to have an immuno-protective effect in TH1-driven autoimmunity diseases. The aim of our article is to review the available research on sex hormone-specific immune modulatory effects, assess its remyelination potential in MS, and suggest a future path for more extensive research on sex hormone as a target for therapeutics in MS.

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Section: Estradiol Synthetic Estrogens and Estriolmentioning

confidence: 99%

The Role of Sex Hormones in Multiple Sclerosis

et al. 2018

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“…Babina and colleagues reported that tamoxifen is capable of inducing a shift from a cellular (T H 1) to a humoral (T H 2) immunity (19,20). Tamoxifen also induces latent TGFb in breast cancer cell lines (21) and prevents maturation of antigen-presenting cells (22).…”

Section: Introductionmentioning

confidence: 99%

L-BLP25 Vaccine plus Letrozole Induces a TH1 Immune Response and Has Additive Antitumor Activity in MUC1-Expressing Mammary Tumors in Mice

Mehta

Wurz

Burich

et al. 2012

Clinical Cancer Research

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Purpose: In this study, we examine the immunomodulatory effects and antitumor activity of tamoxifen and letrozole when combined with the human epithelial mucin (hMUC1)-specific vaccine, L-BLP25, in the hMUC1-expressing mammary tumor (MMT) mouse model.Experimental Design: Dose-finding studies were conducted for both tamoxifen and letrozole. Letrozole and L-BLP25 combination studies used 69 MMT female mice assigned to five groups: untreated, cyclophosphamide þ placebo, cyclophosphamide þ L-BLP25, letrozole 0.8 mg/kg, and cyclophosphamide þ L-BLP25 þ letrozole. Tamoxifen and L-BLP25 combination studies used 48 MMT female mice assigned to five treatment groups: untreated, cyclophosphamide þ placebo, cyclophosphamide þ L-BLP25, tamoxifen 50 mg/kg, and cyclophosphamide þ L-BLP25 þ tamoxifen 50 mg/kg group. Mice were injected subcutaneously with L-BLP25 (10 mg) weekly for 8 weeks. Serum cytokines were serially measured using a Luminex assay, whereas splenocytes at termination were analyzed by ELISpot to determine T-helper (T H )1/T H 2 polarization of immune response.Results: Daily oral doses of 50 and 0.8 mg/kg of tamoxifen and letrozole, respectively, resulted in a significant survival advantage over controls (P < 0.05). A predominant T H 1-polarized immune response in vaccinated mice was seen with or without tamoxifen or letrozole treatments. In the L-BLP25 plus letrozole treatment group, statistically significant (P < 0.05) additive antitumor activity was observed, whereas tamoxifen plus L-BLP25 was not significantly different (P > 0.05). Conclusion:The results of this study show that hormonal therapy does not interfere with L-BLP25-induced predominant T H 1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.

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“…The predictive effect of Tregs on chemotherapy response has been demonstrated in a study where the absolute number of Tregs were found to be declined after chemotherapy administration, while the number of cytotoxic T lymphocytes remained stable, resulting in higher rates of pathological complete response in breast cancer patients treated with neoadjuvant cyclophosphamide [20]. Tamoxifen has also shown to have significant effects on immune system functioning [21]. This suggests that biomarkers involved in tumor immune surveillance and tumor immune escape, may also have a predictive effect on endocrine therapy.…”

Section: Predictive Value Of Hla-g In Breast Cancer Patientsmentioning

confidence: 99%