title: Immune response to a model shared placenta/tumor-associated antigen reduces cancer risk in parous mice.
abstract: During human pregnancy, paternally inherited antigens expressed by the fetal-placental unit can elicit expansion of antigen-specific CD8+ T cells. These cells can persist for years as memory T cells, but their effects on long-term maternal health are unknown. Shared placenta/tumor-associated antigens are expressed by placenta and tumors, but are minimally expressed or absent in normal adult tissues. We hypothesized that maternal T cells elicited against these antigens can alter risk of cancers expressing the same antigen after pregnancy, and tested this in mice using chicken ovalbumin (OVA) as a surrogate shared placenta/tumor antigen. Hemizygous OVA transgenic males were bred to wild-type C57BL/6 females (H2b haplotype) such that the fetuses inherited and expressed OVA. Maternal OVA/H2Kb-specific CD8+ T cells became detectable during gestation, and persisted in some animals for up to 24 weeks. To determine whether these cells might influence growth of OVA-expressing tumors in OVA-bred females, E.G7-OVA thymoma cells were inoculated subcutaneously in OVA-bred, wild-type bred, and virgin females, and monitored for growth. OVA-bred mice had prolonged survival as compared to virgin mice and the progression of tumors was delayed in comparison to wild-type bred and virgin females. Thus, paternally inherited OVA antigen elicited a CD8+ T cell response during pregnancy that was associated with delayed growth of OVA-expressing tumors following pregnancy. These data suggest a possible role of antigen-specific T cells in protecting parous females against tumors bearing shared placenta/tumor antigens.
authors.affiliation: Departments of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Jasti
authors.affiliation: Departments of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Mina
authors.initials: M
authors.lastname: Farahbakhsh
authors.affiliation: Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Petroff
authors.affiliation: Departments of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.|Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.|Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Petroff
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D055354:Exosomes / Q000378:metabolism; D005260:Female; D008223:Lymphoma; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010920:Placenta / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*
chemical_list: D010047:Ovalbumin
keywords: cancer; immunology; placenta; pregnancy