Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer

// Susanne Blank 1, * , Henrik Nienhuser 1, * , Lena Dreikhausen 1 , Leila Sisic 1 , Ulrike Heger 1 , Katja Ott 2 and Thomas Schmidt 1 1 Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany 2 Romed Klinikum Rosenheim, 83022 Rosenheim, Germany * These authors contributed equally to this work Correspondence to: Thomas Schmidt, email: Thomas.Schmidt1@med.uni-heidelberg.de Keywords: cytokines, inflammation, prognosis, response, esophageal cancer Received: January 13, 2017      Accepted: April 17, 2017      Published: May 07, 2017 ABSTRACT Background: Esophageal cancer is often marked by aggressive tumor growth and poor prognosis. Patient groups who benefit from perioperative therapy are not yet defined. The tumor microenvironment and circulating factors as possible predictors of response and prognosis gain interest. This study aimed to investigate cytokines in patients’ serum and tumor tissue with regard to response and prognosis. Results: Median survival between SCC and AC was not different (published previously). Lower levels of CCL11 (Eotaxin-1) and CXCL10 (IP-10) in the tumor tissue were associated with a better prognosis ( p = 0.022; p = 0.002). In the AC subgroup higher concentrations of TGF-β3 in serum and corresponding tumor tissue were associated with adverse prognosis ( p = 0.035; p = 0.006). An association with histopathological response was found for IL-12(p70) and CXCL10 in patients’ sera ( p = 0.041; p = 0.032). The tissue levels of TGF-β1 and TGF-β2 were significantly lower in histopathological responders than in nonresponders ( p = 0.033; p = 0.007). A similar trend was seen for TGF-β3, without statistical significance ( p = 0.097). Materials and Methods: Preoperative serum samples and corresponding tumor tissue ( n = 54), only serum ( n = 20) or only tissue ( n = 4) were collected from patients undergoing surgery for cT3/4 esophageal squamous cell cancer (SCC) ( n = 34) and adenocarcinoma (AC) ( n = 44). All samples were taken after neoadjuvant treatment. All patients received perioperative chemo(radio)therapy. Cytokine levels of 17 different cytokines were measured by multiplex immunoassay and correlated with clinicopathological factors. Conclusions: Two chemokines (CCL11 and CXCL10) in posttherapeutic tumor tissue were associated with prognosis in patients with esophageal cancer, lower levels indicating a better prognosis. Lower levels of TGF-β were associated with better response and prognosis in patients with AC.