Year: 2024
Type: article
Abstract: Breast cancer is commonly thought of as a "women's disease". However, men are increasingly diagnosed with the disease, and their mortality rates are disparately higher than those of female patients. The abundance and composition of the immune microenvironment are determinants of breast cancer progression and survival. It is well documented that there are sex-specific differences in the immune response to several diseases, including various cancers. However, the effects of these differences in the context of breast cancer remain to be explored. This study demonstrates sex differences in the hormonal and immune landscape of the MMTV-PyMT transgenic murine model of female and male ER+ breast cancer using single-cell RNA sequencing (scRNA-Seq), whole-slide immunohistochemistry, and flow cytometry. Mammary tumors of transgenic male mice had increased estrogen receptor alpha expression and enriched nuclear binding signatures compared to female tumors. In the tumor immune compartment, male mice had lower intratumoral leukocyte infiltration. Yet, scRNA-Seq analysis reveals a more immunostimulatory microenvironment and increased antitumor immune populations in the primary and metastatic lungs as compared to transgenic females. Despite a more favorable innate immune profile, the metastatic burden was increased in male mice. Our data support a sex-dependent immune response in mammary carcinoma associated with the tumor, and likely host, hormonal environment. With emerging therapeutics targeting the tumor immune microenvironment, characterizing immune profiles is critical for optimizing their use in all breast cancer patients.
Institutions: Vanderbilt University, St. Jude Children's Research Hospital
Language: English
Topic: Male Breast Health Studies
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,296
Funders: National Science Foundation, Vanderbilt University, METAvivor, Vanderbilt University Medical Center, National Institutes of Health, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1328305094, G1344704808, The COVID-19 and Cancer Consortium: NCI Administrative Supplement to P30 Cancer Center Support Grant (CCSG), G2268269956, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G3433274139, CORE GRANT IN VISION RESEARCH, G4039831958, Graduate Research Fellowship Program (GRFP), G580900752, G5853943267, G6297262231, G725763919, G7520984233, VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced Genomics, G7938301486, G8531250409, Molecular and Cellular Basis for Digestive Diseases, G949362299, G978377415
OpenAlex ID: W4405113940