Standard treatments induce antigen-specific immune responses in prostate cancer.
OBJECTIVE
Prostate tumors express antigens that are recognized by the immune system in a significant proportion of patients; however, little is known about the effect of standard treatments on tumor-specific immunity. Radiation therapy induces expression of inflammatory and immune-stimulatory molecules, and neoadjuvant hormone therapy causes prominent T-cell infiltration of prostate tumors. We therefore hypothesized that radiation therapy and hormone therapy may initiate tumor-specific immune responses.


METHODS
Pretreatment and posttreatment serum samples from 73 men with nonmetastatic prostate cancer and 50 cancer-free controls were evaluated by Western blotting and SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen arrays to examine whether autoantibody responses to tumor proteins arose during the course of standard treatment.


RESULTS
Western blotting revealed the development of treatment-associated autoantibody responses in patients undergoing neoadjuvant hormone therapy (7 of 24, 29.2%), external beam radiation therapy (4 of 29, 13.8%), and brachytherapy (5 of 20, 25%), compared with 0 of 14 patients undergoing radical prostatectomy and 2 of 36 (5.6%) controls. Responses were seen within 4 to 9 months of initiation of treatment and were equally prevalent across different disease risk groups. Similarly, in the murine Shionogi tumor model, hormone therapy induced tumor-associated autoantibody responses in 5 of 10 animals. In four patients, SEREX immunoscreening of a prostate cancer cDNA expression library identified several antigens recognized by treatment-associated autoantibodies, including PARP1, ZNF707 + PTMA, CEP78, SDCCAG1, and ODF2.


CONCLUSIONS
We show for the first time that standard treatments induce antigen-specific immune responses in prostate cancer patients. Thus, immunologic mechanisms may contribute to clinical outcomes after hormone and radiation therapy, an effect that could potentially be exploited as a practical, personalized form of immunotherapy.
Nesslinger
Nancy J
NJ
Trev and Joyce Deeley Research Centre, BC Cancer Agency-Vancouver Island Centre, Victoria, British Columbia, Canada.
Sahota
Robert A
RA
Stone
Brad
B
Johnson
Kayli
K
Chima
Navraj
N
King
Caitlin
C
Rasmussen
Devon
D
Bishop
Darcy
D
Rennie
Paul S
PS
Gleave
Martin
M
Blood
Paul
P
Pai
Howard
H
Ludgate
Charles
C
Nelson
Brad H
BH
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000187:drug effects / Q000528:radiation effects; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood* / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D001918:Brachytherapy; D015723:Gene Library; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D011878:Radiotherapy
D000726:Androgen Antagonists; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D001323:Autoantibodies