From the article:
Conejo-Garcia and colleagues found that estrogen signaling is closely linked to both the accumulation and activity of myeloid-derived suppressor cells (MDSCs), a set of immune cells associated with tumors treatment resistance. Estrogen enables immunosuppression in a two-pronged approach involving MDSCs. First, the estrogen drives the mobilization of MSDCs. Then, at the same time, it makes a subset of the MDSCs more immunosuppressive in vivo. Estrogen supplementation accelerated the growth of multiple models estrogen-insensitive tumors in immunocompetent animals, while ablating estrogen production by resecting the ovaries boosted anti-tumor immunity and delayed malignant progression. Importantly, differences in tumor progression disappeared in immunodeficient mice, demonstrating that estrogen-mediated acceleration of tumor growth depends on dampening protective anti-tumor immunity.
They also demonstrated how ERα is responsible for enhancing the activity of multiple pathways that are already associated with cancer development. This estrogen receptor activated the STAT3 pathway, which has already been linked to cancer cell survival and the expansion of MDSCs in cancer-bearing hosts. It was also able to activate this pathway by enhancing the activity of JAK2 and SRC, two proteins linked to cancer development and immune response.
These cancer pathways are activated in a variety of inflammatory cancers in non-tumor cells, such as breast cancer, ovarian cancer, and melanoma. Since estrogen is present not just pre-menopausal women but men and post-menopausal women as well, the authors propose that investigating anti-estrogen therapeutic strategies could lead to new treatments for a variety of cancers. This strategy could halt the mobilization of MDSCs and tumor initiation.