The Effects of Tamoxifen on Tolerogenic Cells in Cancer

Abstract

Tamoxifen (TAM) is the most prescribed selective estrogen receptor modulator (SERM) to treat hormone-receptor-positive breast cancer patients and has been used for more than 20 years. Its role as a hormone therapy is well established; however, the potential role in modulating tolerogenic cells needs to be better clarified. Infiltrating tumor-microenvironment-regulatory T cells (TME-Tregs) are important as they serve a suppressive function through the transcription factor Forkhead box P3 (Foxp3). Abundant studies have suggested that Foxp3 regulates the expression of several genes (CTLA-4, PD-1, LAG-3, TIM-3, TIGIT, TNFR2) involved in carcinogenesis to utilize its tumor suppressor function through knockout models. TAM is indirectly concomitant via the Cre/loxP system by allowing nuclear translocation of the fusion protein, excision of the floxed STOP cassette and heritable expression of encoding fluorescent protein in a cohort of cells that express Foxp3. Moreover, TAM administration in breast cancer treatment has shown its effects directly through MDSCs by the enrichment of its leukocyte populations, such as NK and NKT cells, while it impairs the differentiation and activation of DCs. However, the fundamental mechanisms of the reduction of this pool by TAM are unknown. Here, we review the vital effects of TAM on Tregs for a precise mechanistic understanding of cancer immunotherapies.

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat

“…Another type of combination has been proposed in a phase II clinical study against hormone-resistant breast cancer (BC) [ 113 ], which is a type of BC that does not respond to treatment with hormones such as tamoxifen. The latter is a drug used to treat and prevent BC by inhibiting the effects of estrogen on breast tissue, which can slow or inhibit the growth of breast tumor cells that depend on estrogen to develop [ 132 ]. In fact, 43 patients with metastatic BC who had progressed on hormone therapy were recruited for this trial.…”

RNA Modifications Meet Tumors

“…Tamoxifen (TAM) is the most prescribed selective estrogen receptor modulator (SERM) for hormone receptor positive breast cancer patients. 154 A recent study found that the protein expression level of ATF3 in tamoxifen resistant (TamR) MCF-7 cells was significantly higher than that in corresponding parent cancer cells. Further research found that m 6 A-modified ATF3 could regulate the resistance of breast cancer cells to tamoxifen.…”