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The Impact of Estrogen in the Tumor Microenvironment
Ashwin Somasundaram1,2,3, Natalie J Rothenberger1,4, Laura P Stabile5,6
1Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract:
Tumor immune escape is now a hallmark of cancer development, and therapies targeting these pathways have emerged as standard of care. Specifically, immune checkpoint signal blockade offers durable responses and increased overall survival. However, the majority of cancer patients still do not respond to checkpoint blockade immune therapy leading to an unmet need in tumor immunology research. Sex-based differences have been noted in the use of cancer immunotherapy suggesting that sex hormones such as estrogen may play an important role in tumor immune regulation. Estrogen signaling already has a known role in autoimmunity, and the estrogen receptor can be expressed across multiple immune cell populations and effect their regulation. While it has been well established that tumor cells such as ovarian carcinoma, breast carcinoma, and even lung carcinoma can be regulated by estrogen, research into the role of estrogen in the regulation of tumor-associated immune cells is still emerging. In this chapter, we discuss the role of estrogen in the tumor immune microenvironment and the possible immunotherapeutic implications of targeting estrogen in cancer patients.
Insights
Estrogen influences the tumor immune microenvironment, impacting cancer immunotherapy effectiveness. Targeting estrogen may offer new treatment strategies for patients unresponsive to current immune checkpoint therapies.
Area of Science:
- Oncology
- Immunology
- Endocrinology
Background:
- Tumor immune escape is a key aspect of cancer development.
- Immune checkpoint blockade therapy improves outcomes but has limited efficacy for many patients.
- Sex-based differences in immunotherapy response suggest a role for sex hormones like estrogen.
Purpose of the Study:
- To explore the role of estrogen in regulating the tumor immune microenvironment.
- To discuss the potential of targeting estrogen for cancer immunotherapy.
Main Methods:
- Review of existing literature on estrogen signaling, immune cells, and cancer.
- Analysis of estrogen receptor expression in tumor-associated immune cells.
- Discussion of estrogen's known effects on various cancer types (ovarian, breast, lung).
Main Results:
- Estrogen signaling affects multiple immune cell populations.
- Estrogen receptor is expressed on various immune cells, influencing their function.
- Estrogen is known to regulate tumor cells in several cancer types.
Conclusions:
- Estrogen plays a significant role in the tumor immune microenvironment.
- Targeting estrogen pathways presents a potential novel immunotherapeutic strategy for cancer treatment.
- Further research is needed to elucidate estrogen's precise mechanisms in tumor immunology.
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