Pregnancy impacts the maternal immune system and breast cancer risk, but whether these effects are related is unknown. Many women are immunologically primed to fetal antigens during pregnancy due to the unique expression of paternally- inherited antigens by the fetus. However, whether this priming has any consequence on subsequent progression of diseases in women is unknown. Tumor antigens are proteins that have limited expression in normal adult tissues, but are strongly expressed in many cancers, including cancer of the breast. Because of their ability to induce immunity, there is strong scientific and medical interest in exploiting this property for development of anti-cancer vaccines. Despite their restricted expression patterns, several, which we call shared placenta/tumor antigens, are highly expressed in the placenta. Investigators have long speculated that trophoblast cells and tumor cells share similarities, but the immunologic relationship between shared placenta/tumor antigens, breast cancer, and pregnancy are completely unknown. In this proposal, we explore the hypothesis that shared tumor/placenta antigens are immunogenic during pregnancy. These experiments serve as critical proof of concept experiments, with which we can further explore the long term hypothesis that immune priming to shared placenta tumor antigens during pregnancy alter breast cancer risk in parous women. To determine whether the placenta primes the maternal immune system against shared placenta/tumor antigens, we propose the following Specific Aims: 1. Determine whether the murine maternal immune system is primed to shared tumor/placenta antigens. 2. Test women for evidence of sensitization to shared placenta/tumor antigens. To our knowledge, this is the first time that a long-term consequence of the physiologically normal maternal immune response to fetal antigens will be considered in light of a critical clinical problem: women's cancer. In the long-term, this work could profoundly impact our understanding of why parity changes risk of breast cancer, and lead to insights into novel cancer prevention and therapeutic strategies.

Public Health Relevance

Pregnancy impacts the maternal immune system and breast cancer risk, but whether these effects are related is unknown. Here we will test the hypothesis that mothers are sensitized to antigens shared by the placenta and breast cancer cells. Experiments will lead to critical proof of concept data that will allow further study of the impact of pregnancy-mediated changes in the maternal immune system on long-term breast cancer risk in women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD083058-01A1
Application #
9316903
Study Section
Pregnancy and Neonatology Study Section (PN)
Program Officer
Ilekis, John V
Project Start
2017-05-18
Project End
2019-04-30
Budget Start
2017-05-18
Budget End
2018-04-30
Support Year
1
Fiscal Year
2017
Total Cost
$232,500
Indirect Cost
$82,500
Name
Michigan State University
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824