title: Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.
abstract: BACKGROUND
  We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression.
  
  
  METHODS
  Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine levels with lenalidomide treatment effect. Estimates were obtained using generalized estimating equations. Changes in circulating anti-prostate antibodies were evaluated using a high-throughput immunoblot technique.
  
  
  RESULTS
  Treatment with lenalidomide was associated with global changes in immunoreactivity to a number of prostate-associated antigens, as well as with changes in circulating levels of the T(H) 2 cytokines IL-4, IL-5, IL-10, and IL-13. Disease progression in treated patients was associated with an increase in circulating IL-8 levels, while IL-8 levels decreased significantly in non-progressors.
  
  
  CONCLUSIONS
  Lenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti-prostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL-8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials.
authors: Johns Hopkins Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors: Daniel J
authors: DJ
authors: Zabransky
authors: Heath A
authors: HA
authors: Smith
authors: Christopher J
authors: CJ
authors: Thoburn
authors: Marianna
authors: M
authors: Zahurak
authors: Daniel
authors: D
authors: Keizman
authors: Michael
authors: M
authors: Carducci
authors: Mario A
authors: MA
authors: Eisenberger
authors: Douglas G
authors: DG
authors: McNeel
authors: Charles G
authors: CG
authors: Drake
authors: Emmanuel S
authors: ES
authors: Antonarakis
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016209:Interleukin-8 / Q000378:metabolism*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016209:Interleukin-8; D013792:Thalidomide; D017430:Prostate-Specific Antigen; D000077269:Lenalidomide