Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer

Daniel J. Zabransky, Heath A. Smith, Christopher J. Thoburn, Marianna Zahurak, Daniel Keizman, Michael A Carducci, Mario Eisenberger, Douglas G. McNeel, Charles G. Drake, Emmanuel Antonarakis

Research output: Contribution to journalArticle

Abstract

Background: We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25mg 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 H2 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.

Original languageEnglish (US)
Pages (from-to)487-498
Number of pages12
JournalProstate
Volume72
Issue number5
DOIs
StatePublished - Apr 2012

Fingerprint

Interleukin-8
Prostate
Anti-Idiotypic Antibodies
Prostatic Neoplasms
Cytokines
Disease Progression
Interleukin-13
Interleukin-5
Interleukin-4
Interleukin-10
lenalidomide
Therapeutics
Biomarkers
Antigens
Serum

Keywords

  • antibody
  • cytokine
  • IL-8
  • lenalidomide
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer. / Zabransky, Daniel J.; Smith, Heath A.; Thoburn, Christopher J.; Zahurak, Marianna; Keizman, Daniel; Carducci, Michael A; Eisenberger, Mario; McNeel, Douglas G.; Drake, Charles G.; Antonarakis, Emmanuel.

In: Prostate, Vol. 72, No. 5, 04.2012, p. 487-498.

Research output: Contribution to journalArticle

Zabransky, Daniel J. ; Smith, Heath A. ; Thoburn, Christopher J. ; Zahurak, Marianna ; Keizman, Daniel ; Carducci, Michael A ; Eisenberger, Mario ; McNeel, Douglas G. ; Drake, Charles G. ; Antonarakis, Emmanuel. / Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer. In: Prostate. 2012 ; Vol. 72, No. 5. pp. 487-498.
@article{55402854c21b4f0f91927f1f186c4f90,
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 25mg 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 H2 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.",
keywords = "antibody, cytokine, IL-8, lenalidomide, prostate cancer",
author = "Zabransky, {Daniel J.} and Smith, {Heath A.} and Thoburn, {Christopher J.} and Marianna Zahurak and Daniel Keizman and Carducci, {Michael A} and Mario Eisenberger and McNeel, {Douglas G.} and Drake, {Charles G.} and Emmanuel Antonarakis",
year = "2012",
month = "4",
doi = "10.1002/pros.21449",
language = "English (US)",
volume = "72",
pages = "487--498",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer

AU - Zabransky, Daniel J.

AU - Smith, Heath A.

AU - Thoburn, Christopher J.

AU - Zahurak, Marianna

AU - Keizman, Daniel

AU - Carducci, Michael A

AU - Eisenberger, Mario

AU - McNeel, Douglas G.

AU - Drake, Charles G.

AU - Antonarakis, Emmanuel

PY - 2012/4

Y1 - 2012/4

N2 - Background: We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25mg 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 H2 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.

AB - Background: We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25mg 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 H2 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.

KW - antibody

KW - cytokine

KW - IL-8

KW - lenalidomide

KW - prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=84857507764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857507764&partnerID=8YFLogxK

U2 - 10.1002/pros.21449

DO - 10.1002/pros.21449

M3 - Article

VL - 72

SP - 487

EP - 498

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 5

ER -