Comment on ‘Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma’

Abstract

Academic Department of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, GlasgowG31 2ER, UKSir,We read with interest the work of Kantola and coworkers whoexamined the patterns of alterations of serum cytokine concentrationsbetween normal controls and 148 patients newly diagnosed withcolorectal cancer. Although in the main body of the paper theydemonstrated clearly that the pr esence of colorectal cancer wasassociated with extensive alterations in the serum cytokine environment,it was also of interest that, within the colorectal cancer group, there wereimportant findings to which the authors made little comment.In particular, the data given within Tables 3 and 4 andSupplementary Tables 4, 5, 6, 7, 8, and 9 give a unique insight intothe relationship between the serum cytokine alterations and thetumour-host systemic inflammatory response in patients withcolorectal cancer. From these Tables, it is clear that sex, tumoursite, and N-stage had little association with the serum cytokinealterations reported. Furthermore, increasing T-stage was onlyassociated with a significant increase in IL-6, IL-8, and MCP-1;increasing grade was only associated with a significant increase inIL-6 and IL-8; while the presence of metastasis was associated witha significant increase in IL-4, IL-6, IL-7, IL-8, MCP-1, and PDGF-BB. In contrast, the presence of a systemic inflammatory response,as evidenced by the modified Glasgow Prognostic Score (mGPS),was significantly associated with IL-1ra, IL-6, IL-7, IL-8, IL-9,IL-12, IFN-g, IP-10, MCP-1, MIP-1B, and PDGF-BB. Takentogether, these results would suggest that, in terms of influencingserum cytokine alterations, tumour-based factors have less effectthan the activation of the systemic inflammatory response. Indeed,this is consistent with the report that the majority of patients donot resolve their systemic inflammatory response, followingpotentially curative surgery (McMillan et al, 2003; Guthrie et al,2013) and the established prognostic value of the systemicinflammatory response in patients with colorectal cancer, beforesurgery (Roxburgh and McMillan, 2010).Another interesting aspect of the work of Kantola andcolleagues is that the association between mGPS and the serumcytokine alterations provides new insight into the inflammatorycells associated with the upregulation of the systemic inflammatoryresponse in patients with colorectal cancer. With the exceptionof macrophages, few inflammatory cells can produce such aspectrum of cytokines and growth factors, and this is consistentwith recent reports that macrophages are abundant in tumourmicroenvironments even in the absence of other inflammatorycells (Mohammed et al, 2012); (Richards et al, 2012a). Interest-ingly, the above findings are consistent with the hypothesis thattumour necrosis (increases with T stage) has an important role inlinking local and systemic inflammatory responses in patients withcolorectal cancer (Richards et al, 2012b).It has long been recognised that tumour-associated macro-phages localise to hypoxic regions of the tumour microenviron-ment. Therefore, it is plausible that the relative density ofmacrophages (perhaps M2) are important in such cytokinealterations and the elaboration of the systemic inflammatoryresponse in patients with colorectal cancer. Alternatively, recentwork has suggested that an accumulation of myeloid-derivedsuppressor cells in the tumour microenvironment may beimportant in these observations. Irrespectively, the abovecomments should encourage the authors to extend their studiesin this area.REFERENCES