Cytokine concentration in peripheral blood of patients with colorectal cancer

Introduction The 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. Methods Peripheral 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. Results In 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. Discussion Different 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.

[1]  L. Naldini,et al.  Gene-based delivery of immune-activating cytokines for cancer treatment. , 2023, Trends in molecular medicine.

[2]  F. Izzo,et al.  Plasma metabolomics, lipidomics and cytokinomics profiling predict disease recurrence in metastatic colorectal cancer patients undergoing liver resection , 2023, Frontiers in Oncology.

[3]  T. Wieder,et al.  The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies , 2022, Cells.

[4]  A. Vincent-Salomon,et al.  Definition of a novel breast tumor-specific classifier based on secretome analysis , 2022, Breast cancer research : BCR.

[5]  Yanyuan Wu,et al.  Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China , 2022, Frontiers in Immunology.

[6]  Xiang Xue,et al.  The Role of Inflammatory Mediators in Colorectal Cancer Hepatic Metastasis , 2022, Cells.

[7]  Chi Wang,et al.  Ketogenesis attenuates KLF5-dependent production of CXCL12 to overcome the immunosuppressive tumor microenvironment in colorectal cancer. , 2022, Cancer research.

[8]  Sheng-Nan Jia,et al.  Chemokines in colon cancer progression. , 2022, Seminars in cancer biology.

[9]  F. Balkwill,et al.  Harnessing cytokines and chemokines for cancer therapy , 2022, Nature Reviews Clinical Oncology.

[10]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[11]  R. Pfeiffer,et al.  Circulating Inflammation Markers and Pancreatic Cancer Risk: A Prospective Case-cohort Study in Japan. , 2021, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[12]  Qiushui He,et al.  Dysbiosis of Gut Microbiota Promotes Hepatocellular Carcinoma Progression by Regulating the Immune Response , 2021, Journal of immunology research.

[13]  Lei Wu,et al.  Inflammation and tumor progression: signaling pathways and targeted intervention , 2021, Signal Transduction and Targeted Therapy.

[14]  F. Greten,et al.  The inflammatory pathogenesis of colorectal cancer , 2021, Nature Reviews Immunology.

[15]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[16]  I. Baranowska-Bosiacka,et al.  CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4 , 2020, International journal of molecular sciences.

[17]  Yan Zhang,et al.  The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy , 2020, Gastroenterology report.

[18]  Dawang Zhou,et al.  Ectosomal PKM2 Promotes HCC by Inducing Macrophage Differentiation and Remodeling the Tumor Microenvironment. , 2020, Molecular cell.

[19]  Takehiro Hirano,et al.  Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis , 2020, International journal of molecular sciences.

[20]  D. Rubin,et al.  Cumulative Histologic Inflammation Predicts Colorectal Neoplasia in Ulcerative Colitis: A Validation Study. , 2020, Inflammatory bowel diseases.

[21]  A. Chinnaiyan,et al.  CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy , 2019, Nature.

[22]  A. Chinnaiyan,et al.  CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy , 2019, Nature.

[23]  Jeffrey S. Morris,et al.  Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer , 2019, British Journal of Cancer.

[24]  T. Waldmann.  Cytokines in Cancer Immunotherapy. , 2018, Cold Spring Harbor perspectives in biology.

[25]  D. di Bernardo,et al.  Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer , 2018, Cell reports.

[26]  M. Zheng,et al.  CCR6 promotes tumor angiogenesis via the AKT/NF-κB/VEGF pathway in colorectal cancer. , 2018, Biochimica et biophysica acta. Molecular basis of disease.

[27]  G. Jobin,et al.  Association Between Natural Killer Cell Activity and Colorectal Cancer in High-Risk Subjects Undergoing Colonoscopy. , 2017, Gastroenterology.

[28]  Maayan Levy,et al.  Microbiome, metabolites and host immunity. , 2017, Current opinion in microbiology.

[29]  S. Górska,et al.  Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon , 2016, Cancer Immunology, Immunotherapy.

[30]  P. Allavena,et al.  Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient , 2016, Journal of Immunotherapy for Cancer.

[31]  P. Allavena,et al.  Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer , 2016, PloS one.

[32]  A. Crucitti,et al.  Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors , 2015, Cancer biology & therapy.

[33]  K. Matsushima,et al.  CCR4 and its ligands: from bench to bedside. , 2015, International immunology.

[34]  M. De la Fuente,et al.  Chronic Inflammation and Cytokines in the Tumor Microenvironment , 2014, Journal of immunology research.

[35]  James H Doroshow,et al.  Molecular mechanisms underlying chronic inflammation-associated cancers. , 2014, Cancer letters.

[36]  A. Gamian,et al.  Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. , 2013, Cancer letters.

[37]  B. Lippitz,et al.  Cytokine patterns in patients with cancer: a systematic review. , 2013, The Lancet. Oncology.

[38]  Y. Surh,et al.  Resolution of inflammation as a novel chemopreventive strategy , 2013, Seminars in Immunopathology.

[39]  T. Hagemann,et al.  Cancer-Related Inflammation , 2012, Journal of Clinical Immunology.

[40]  Michael Karin,et al.  Inflammation and colon cancer. , 2010, Gastroenterology.

[41]  A. Richmond,et al.  Chemokines and chemokine receptors: new insights into cancer-related inflammation. , 2010, Trends in molecular medicine.

[42]  R. Medzhitov.  Origin and physiological roles of inflammation , 2008, Nature.

[43]  S. Nakagawa,et al.  CC‐chemokine ligand 17 gene therapy induces tumor regression through augmentation of tumor‐infiltrating immune cells in a murine model of preexisting CT26 colon carcinoma , 2007, International journal of cancer.

[44]  G. Gaedicke,et al.  Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. , 2007, Cancer research.

[45]  L. Coussens,et al.  Inflammation and cancer , 2002, Nature.

[46]  Alberto Mantovani,et al.  Inflammation and cancer: back to Virchow? , 2001, The Lancet.

[47]  L. Wagner,et al.  Monocyte chemoattractant protein (MCP)-4 expression in the airways of patients with asthma. Induction in epithelial cells and mononuclear cells by proinflammatory cytokines. , 2000, American journal of respiratory and critical care medicine.

[48]  Q. Hamid,et al.  Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. , 1996, Journal of immunology.

[49]  A. Chinnaiyan,et al.  FADD/MORT1 Is a Common Mediator of CD95 (Fas/APO-1) and Tumor Necrosis Factor Receptor-induced Apoptosis (*) , 1996, The Journal of Biological Chemistry.