Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen.
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.
Drake
Charles G
CG
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA. cdrake@jhmi.edu
Doody
Amy D H
AD
Mihalyo
Marianne A
MA
Huang
Ching-Tai
CT
Kelleher
Erin
E
Ravi
Sowmya
S
Hipkiss
Edward L
EL
Flies
Dallas B
DB
Kennedy
Eugene P
EP
Long
Meixiao
M
McGary
Patrick W
PW
Coryell
Lee
L
Nelson
William G
WG
Pardoll
Drew M
DM
Adler
Adam J
AJ
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
D000728:Androgens; D000957:Antigens, Viral, Tumor