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

Abstract

BackgroundEsophageal 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.ResultsMedian 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 MethodsPreoperative 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.ConclusionsTwo 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.

Dietary inflammatory index and risk of oesophageal cancer in Xinjiang Uyghur Autonomous Region, China

“…Both histopathologic subtypes are well known to be associated with inflammation. The effect of chronic inflammation in the growth of ESCC is well-established (31,(50)(51)(52) . Similarly, the influence of inflammation in the process of malignant transformation in the sequence from Barrett's oesophagus to frank adenocarcinoma is particularly well defined (53)(54)(55) , including the effect of oxidative stress, which is intimately associated with both diet and inflammatory response, in relation to reflux oesophagitis (56) .…”

Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas

“…factors in our cohort. Blank et al also failed to demonstrate any associations with clinicopathological values and systemic IL-6 levels in a recent analysis [16]. The latter study investigated EACs after neoadjuvant therapy only, hence the systemic immune status might have already been altered.…”

“…Both interleukins have been reported to play a role in esophageal squamous cell carcinomas (ESCC) and other gastrointestinal malignancies like gastric cancers [8][9][10][11][12][13][14][15]. However in EACs conflicting results have been reported [16][17][18]. On the other hand, anti-inflammatory cytokines like IL-4 and IL-10 have a predominantly regulatory function in the immune system [19,20].…”

CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation – A target for novel cancer therapy

“…The reduction of not only CXCR3, but also of CXCL9 and CXCL10 could suppress cancer metastatic frequencies in melanoma,[55] colon cancer,[7, 52, 56] and breast cancer models[57, 58]. There is a consensus among some groups about the association between CXCL9 [59, 60] and CXCL10 [54, 61] expression and poor prognosis or negative response to existing therapy, whereas others report that CXCL9 [62–64] and CXCL10 [65, 66] are related to opposite results. These differences in reports may be due to complex relationship between each ligand depending on the cancer types.…”