title: Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen.
abstract: To understand the T cell response to prostate cancer, we created transgenic mice that express a model antigen in a prostate-restricted pattern and crossed these animals to TRAMP mice that develop spontaneous prostate cancer. Adoptive transfer of prostate-specific CD4 T cells shows that, in the absence of prostate cancer, the prostate gland is mostly ignored. Tumorigenesis allows T cell recognition of the prostate gland--but this recognition is tolerogenic, resulting in abortive proliferation and ultimately in hyporesponsiveness at the systemic level. Androgen ablation (the most common treatment for metastatic prostate cancer) was able to mitigate this tolerance--allowing prostate-specific T cells to expand and develop effector function after vaccination. These results suggest that immunotherapy for prostate cancer may be most efficacious when administered after androgen ablation.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA. cdrake@jhmi.edu
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.forename: Amy D H
authors.initials: AD
authors.lastname: Doody
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Mihalyo
authors.forename: Ching-Tai
authors.initials: CT
authors.lastname: Huang
authors.forename: Erin
authors.initials: E
authors.lastname: Kelleher
authors.forename: Sowmya
authors.initials: S
authors.lastname: Ravi
authors.forename: Edward L
authors.initials: EL
authors.lastname: Hipkiss
authors.forename: Dallas B
authors.initials: DB
authors.lastname: Flies
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Kennedy
authors.forename: Meixiao
authors.initials: M
authors.lastname: Long
authors.forename: Patrick W
authors.initials: PW
authors.lastname: McGary
authors.forename: Lee
authors.initials: L
authors.lastname: Coryell
authors.forename: William G
authors.initials: WG
authors.lastname: Nelson
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Adler
mesh_terms: D019264:Adoptive Transfer; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D000728:Androgens; D000957:Antigens, Viral, Tumor