title: Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy.
abstract: Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation.
  
  
  
  We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed.
  
  
  
  Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed.
  
  
  
  Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes.
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.|Division of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Chetan P
authors.initials: CP
authors.lastname: Offord
authors.affiliation: Department of Urology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Department of Radiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Kuribayashi
authors.affiliation: Department of Urology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Division of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.|Diagnostic Pathology, Ritsuzankai Iida Hospital, Iida, Nagano 395-0056, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shimojo
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanno
authors.affiliation: Program for Evolutionary Dynamics, Harvard University, One Brattle Square, Suite 6, Cambridge, MA 02138-3758, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bozic
authors.affiliation: Program for Evolutionary Dynamics, Harvard University, One Brattle Square, Suite 6, Cambridge, MA 02138-3758, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Nowak
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Bajzer
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.|Division of Hematology, Mayo Clinic, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
mesh_terms: D000368:Aged; D001918:Brachytherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D017430:Prostate-Specific Antigen