The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression

Abstract

Background Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGF 1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-speciWc survival. Materials and methods Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGF 1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their conWdence intervals were estimated, and Akaike's information criterion was calculated for model comparison. ResultsThe predictive ability of a model for prostate cancer survival more than doubled when TGF 1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively). Conclusion IL-7 and TGF 1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.

Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer

“…We identified an important type I IFN/IL7 axis involved in the negative control of protumoral gdT17 cells in solid tumors. Those findings could also be potentially relevant in the context of human breast cancer regarding that elevated expression of IL7 is considered usually as a poor prognosis for tumor progression in patients (21)(22)(23). Considering the pivotal role of IL17A in regulating tumor growth, angiogenesis, and metastasis during breast cancer in the mouse model, our study suggests that the implementation of novel combined strategies to both specifically activate type I IFN and/or neutralize IL7 activities could benefit the field of immunotherapy research against solid tumors.…”

“…Interestingly, the level of IL7 increases with tumor progression in peritoneal exudates from ovarian cancer-bearing mice (16). Moreover, levels of IL7 have been associated with poor prognosis in patients with prostate cancer (21,22) and positively correlated with tumor aggressiveness in patients with breast cancers (23). In view of this, it is tempting to speculate that the putative regulatory functions of tumor-derived IL7 on gdT17 cell biology can somehow explain the phenotypes stated above.…”

Molecular Profiling Predicts the Existence of Two Functionally Distinct Classes of Ovarian Cancer Stroma

“…Since a compatible receptor of this inhibitor (FGFR3) is expressed in Cepi, CS 2 may be a more conducive microenvironment for tumor growth than CS 1 . The interleukin-7 (IL7) ligand has been previously implicated as an inducer of tumor growth in lymphoblastic leukemia [10], prostate cancer [11], breast cancer [12], and colorectal cancer [13]. IL7 is expressed in CS 2 but not in CS 1 , again suggesting that CS 2 may be a more conducive microenvironment for tumor growth than CS 1 .…”

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

“…Transforming growth factor (TGF-b) has been shown to play an important role in controlling bone metastasis of prostate cancer (Massague, 2008;Sato et al, 2008;Nguyen et al, 2009;Juarez and Guise, 2011). Prostate tumor cells are known to produce TGF-b 1 (Barrett et al, 2006), and high levels of TGF-b 1 in the blood circulation, and TGF-b-dependent SMAD phosphorylation pathways in the tumors are poor prognostic markers of prostate cancer (Shariat et al, 2001;Lu et al, 2007;Schroten et al, 2011). Therefore, targeting TGF-b is an attractive approach for the treatment of bone metastases (Iyer et al, 2005;Massague, 2008;Sato et al, 2008;Jones et al, 2009;Nguyen et al, 2009;Juarez and Guise, 2011;Mishra et al, 2011).…”