Cytokine concentration in peripheral blood of patients with colorectal cancer

Abstract

IntroductionThe role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared.MethodsPeripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples.ResultsIn peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1β, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis.DiscussionDifferent types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.

Macrophage Inflammatory Proteins (MIPs) Contribute to Malignant Potential of Colorectal Polyps and Modulate Likelihood of Cancerization Associated with Standard Risk Factors

“…This observation is in line with the finding that methylation of CXCL2 is significantly reduced in colorectal tumors [44], which would alleviate a methylation-depended suppression of CXCL2 transcription [45]. Indeed, CXCL2 upregulation in CRC has been reported [25,28,29,46], although not unanimously [47], and found to reflect patients' clinical outcome and CRC stage [48]. CXCL2 activates the NFκB pathway and NLRP3 inflammasome [14].…”

“…Contrary to M1 macrophages, recruiting other immune cells may support tumor growth. Accordingly, Th2 cells are implicated in tumor promotion, similarly to monocytic and granulocytic MDSC attracted by MIP-2α/CXCL2 [46,49]. Likewise, neutrophils recruited by the chemokine can be steered to differentiate into an immunosuppressive N2 phenotype [33,44,46].…”

“…Accordingly, Th2 cells are implicated in tumor promotion, similarly to monocytic and granulocytic MDSC attracted by MIP-2α/CXCL2 [46,49]. Likewise, neutrophils recruited by the chemokine can be steered to differentiate into an immunosuppressive N2 phenotype [33,44,46]. Moreover, CXCL2 promotes cancer cell proliferation [14,50], migration and interaction with extracellular matrix (ECM) components [50], facilitating liver [14] and peritoneal [50] metastasis.…”

“…CCL19 has been identified by dataset analyses as diagnostic marker, the downregulation of which has 90% accuracy in CRC detection [55]. Still, some authors have reported an upregulation of CCL19 at advanced CRC stages [25,46]. Others, in turn, have linked the chemokine overexpression with better prognosis, given its ability to recruit antitumor immune cells into TME [39,56].…”

Atypical memory B cells increase in the peripheral blood of patients with breast cancer regardless of lymph node involvement

“…Despite all efforts, therapeutic approaches are not completely effective, and the mortality rate remains high [41]. The presence of tumors and immune cells that respond to tumors, as well as their mediators, such as cytokines can be observed in the peripheral blood during tumor development and progression [18,[42][43][44][45]. This suggests that these markers can be utilized for early diagnosis, evaluating patients' response to treatment, and predicting overall survival (OS) [46].…”