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The Role of the Estrogen Pathway in the Tumor Microenvironment

Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA 15232, USA
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 611;
Received: 11 January 2018 / Revised: 13 February 2018 / Accepted: 16 February 2018 / Published: 19 February 2018
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action)
Estrogen receptors are broadly expressed in many cell types involved in the innate and adaptive immune responses, and differentially regulate the production of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms of estrogen signaling are well characterized in multiple carcinomas including breast, ovarian, and lung, recent investigations have identified a potential immune regulatory role of estrogens in the tumor microenvironment. Tumor immune tolerance is a well-established mediator of oncogenesis, with increasing evidence indicating the importance of the immune response in tumor progression. Immune-based therapies such as antibodies that block checkpoint signals have emerged as exciting therapeutic approaches for cancer treatment, offering durable remissions and prolonged survival. However, only a subset of patients demonstrate clinical response to these agents, prompting efforts to elucidate additional immunosuppressive mechanisms within the tumor microenvironment. Evidence drawn from multiple cancer types, including carcinomas traditionally classified as non-immunogenic, implicate estrogen as a potential mediator of immunosuppression through modulation of protumor responses independent of direct activity on tumor cells. Herein, we review the interplay between estrogen and the tumor microenvironment and the clinical implications of endocrine therapy as a novel treatment strategy within immuno-oncology. View Full-Text
Keywords: estrogen; cancer; tumor microenvironment; immunotherapy; immunosuppression estrogen; cancer; tumor microenvironment; immunotherapy; immunosuppression
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Rothenberger, N.J.; Somasundaram, A.; Stabile, L.P. The Role of the Estrogen Pathway in the Tumor Microenvironment. Int. J. Mol. Sci. 2018, 19, 611.

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