Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy
Jessica E Hawley, Samuel Pan, William D Figg, Zoila A Lopez-Bujanda, Jonathan D Strope, David H Aggen, Matthew C Dallos, Emerson A Lim, Mark N Stein, Jianhua Hu, Charles G Drake, Jessica E Hawley, Samuel Pan, William D Figg, Zoila A Lopez-Bujanda, Jonathan D Strope, David H Aggen, Matthew C Dallos, Emerson A Lim, Mark N Stein, Jianhua Hu, Charles G Drake
Abstract
Background: Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.
Methods: Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables.
Results: Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042).
Conclusions: Several innate cytokines were associated with biochemically recurrent prostate cancer.
Keywords: IL-23; IL-8; TNF-α; biochemical recurrence.
Conflict of interest statement
Conflict of Interest Disclosure Statement: CGD is a co-inventor on patents licensed from JHU to BMS, has served as a paid consultant to for Bristol Myers Squibb (BMS), Compugen, Merck, Novartis, Roche-Genentech, Tizona and Werewolf pharmaceuticals, and has received sponsored research funding from the Bristol-Myers Squibb International Immuno-Oncology Network.
© 2019 Wiley Periodicals, Inc.
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Source: PubMed