title: Standard treatments induce antigen-specific immune responses in prostate cancer.
abstract: 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.
authors.affiliation: Trev and Joyce Deeley Research Centre, BC Cancer Agency-Vancouver Island Centre, Victoria, British Columbia, Canada.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Nesslinger
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sahota
authors.forename: Brad
authors.initials: B
authors.lastname: Stone
authors.forename: Kayli
authors.initials: K
authors.lastname: Johnson
authors.forename: Navraj
authors.initials: N
authors.lastname: Chima
authors.forename: Caitlin
authors.initials: C
authors.lastname: King
authors.forename: Devon
authors.initials: D
authors.lastname: Rasmussen
authors.forename: Darcy
authors.initials: D
authors.lastname: Bishop
authors.forename: Paul S
authors.initials: PS
authors.lastname: Rennie
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Paul
authors.initials: P
authors.lastname: Blood
authors.forename: Howard
authors.initials: H
authors.lastname: Pai
authors.forename: Charles
authors.initials: C
authors.lastname: Ludgate
authors.forename: Brad H
authors.initials: BH
authors.lastname: Nelson
mesh_terms: 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
chemical_list: D000726:Androgen Antagonists; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D001323:Autoantibodies