The role of pro-inflammatory cytokines and immune cells in colorectal carcinoma progression

Liu,Huanran; Zhang,Zhen; Tabuchi,Takafumi; Wang,Shouyu; Wang,Jiangning

doi:10.3892/ol.2013.1176

The role of pro-inflammatory cytokines and immune cells in colorectal carcinoma progression

Authors:
- Huanran Liu
- Zhen Zhang
- Takafumi Tabuchi
- Shouyu Wang
- Jiangning Wang
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Affiliations: Department of Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China, Department of Surgery, Kasumigaura Hospital, Tokyo Medical University, Ibaragi 300-0395, Japan, Department of Reparative and Reconstructive Surgery, Luhe Hospital, Capital Medical University, Beijing 101100, P.R. China
Published online on: February 5, 2013 https://doi.org/10.3892/ol.2013.1176
Pages: 1177-1182

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Abstract

Cytokines exhibit a pleiotropic effect in the regulation of the immune cell function, tumor growth and antitumor immune responses. A total of 30 patients with colorectal carcinoma were enrolled on this study and their levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, serum granulocyte colony-stimulating factor (sG-CSF) and serum macrophage colony-stimulating factor (sM-CSF) were measured preoperatively using ELISA. Tumor-infiltrating granulocyte (TIG), tumor-associated macrophage (TAM), G-CSF and M-CSF expression in tumor cells were examined using immunostaining. This study revealed abnormal levels of cytokines in patients, including IL-1β (1/30, 3.3%), IL-6 (16/30 53.3%), IL-81 (15/30, 50%), TNF-α (4/21, 19%), sG-CSF (17/30, 56.7%) and sM-CSF (4/21, 19%). There was a positive linear correlation between IL-6 and sM-CSF (P=0.017, R=0.517). sG-CSF was significantly associated with a deeper tumor invasion (P=0.039) and a more advanced tumor stage (P=0.023). The granulocyte/lymphocyte (G/L) ratio was associated with abnormal levels of sG-CSF. Logistic univariate analysis revealed that TIGs were a risk factor for lymph node metastasis (0.019) and TAMs were a risk factor for depth of invasion (0.029), but this was not confirmed in logistic multivariate analysis. In conclusion, IL-6, IL-8, sM-CSF and sG-CSF may indirectly promote tumor growth, progression and metastasis by changing the leukocyte populations in the blood and the tumor microenvironment.

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1	Schoenfeld J, Jinushi M, Nakazaki Y, et al: Active immunotherapy induces antibody responses that target tumor angiogenesis. Cancer Res. 70:10150–10160. 2010. View Article : Google Scholar : PubMed/NCBI
2	Noori S, Taghikhani M, Hassan ZM, Allameha A and Mostafaei A: Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo. Mol Immunol. 47:1579–1584. 2010. View Article : Google Scholar : PubMed/NCBI
3	Lesterhuis WJ, Punt CJ, Hato SV, et al: Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest. 121:3100–3108. 2011. View Article : Google Scholar : PubMed/NCBI
4	Wieder T, Braumüller H, Kneilling M, Pichler B and Röcken M: T cell-mediated help against tumors. Cell Cycle. 7:2974–2977. 2008. View Article : Google Scholar : PubMed/NCBI
5	Forte G, Sorrentino R, Montinaro A, et al: Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma. J Immunol. 189:2226–2233. 2012. View Article : Google Scholar : PubMed/NCBI
6	Kandasamy M, Bay BH, Lee YK and Mahendran R: Lactobacilli secreting a tumor antigen and IL15 activates neutrophils and dendritic cells and generates cytotoxic T lymphocytes against cancer cells. Cell Immunol. 271:89–96. 2011. View Article : Google Scholar
7	Schwandt A, Garcia JA, Elson P, et al: Clinical and immunomodulatory effects of celecoxib plus interferon-alpha in metastatic renal cell carcinoma patients with COX-2 tumor immunostaining. J Clin Immunol. 31:690–698. 2011. View Article : Google Scholar
8	Yamamoto M, Kamigaki T, Yamashita K, et al: Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer. Oncol Rep. 22:337–343. 2009.PubMed/NCBI
9	Kuper H, Adami HO and Trichopoulos D: Infections as a major preventable cause of human cancer. J Intern Med. 248:171–183. 2000. View Article : Google Scholar : PubMed/NCBI
10	Mareel M and Madani I: Tumour-associated host cells participating at invasion and metastasis: targets for therapy? Acta Chir Belg. 106:635–640. 2006.PubMed/NCBI
11	de Visser KE and Coussens LM: The inflammatory tumor micro-environment and its impact on cancer development. Contrib Microbiol. 13:118–137. 2006.
12	Kenny PA and Bissell MJ: Tumour reversion: correction of malignant behavior by microenvironmental cues. Int J Cancer. 107:688–695. 2003. View Article : Google Scholar : PubMed/NCBI
13	Revoltella RP, Menicagli M and Campani D: Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas. Cytokine. 57:347–359. 2012. View Article : Google Scholar
14	Curran CS, Evans MD and Bertics PJ: GM-CSF production by glioblastoma cells has a functional role in eosinophil survival, activation, and growth factor production for enhanced tumor cell proliferation. J Immunol. 187:1254–1263. 2011. View Article : Google Scholar
15	Liao HH, Wang YC, Chen MC, et al: Down-regulation of granulocyte-macrophage colony-stimulating factor by 3C-like proteinase in transfected A549 human lung carcinoma cells. BMC Immunol. 12:162011. View Article : Google Scholar : PubMed/NCBI
16	Inoue H, Iga M, Nabeta H, et al: Non-transmissible Sendai virus encoding granulocyte macrophage colony-stimulating factor is a novel and potent vector system for producing autologous tumor vaccines. Cancer Sci. 99:2315–2326. 2008. View Article : Google Scholar
17	Ashizawa T, Okada R, Suzuki Y, et al: Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6. Acta Med Okayama. 60:325–330. 2006.PubMed/NCBI
18	Bao B, Ahmad A, Kong D, et al: Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF. PLoS One. 7:e437262012. View Article : Google Scholar
19	Sato T, Omura M, Saito J, Hirasawa A, Kakuta Y, Wakabayashi Y and Nishikawa T: Neutrophilia associated with anaplastic carcinoma of the thyroid: production of macrophage colony-stimulating factor (M-CSF) and interleukin-6. Thyroid. 10:1113–1118. 2000. View Article : Google Scholar : PubMed/NCBI
20	Riesco A: Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 25:135–140. 1970.PubMed/NCBI
21	Atzpodien J, Royston P, Wandert T and Reitz M: DGCIN - German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group: Metastatic renal carcinoma comprehensive prognostic system. Br J Cancer. 88:348–353. 2003. View Article : Google Scholar
22	Négrier S, Escudier B, Gomez F, et al: Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d'Immunothérapie. Ann Oncol. 13:1460–1468. 2002.
23	Donskov F and von der Maase H: Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol. 24:1997–2005. 2006. View Article : Google Scholar : PubMed/NCBI
24	Schmidt H, Suciu S, Punt CJ, et al American Joint Committee on Cancer Stage IV Melanoma; EORTC 18951: Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol. 25:1562–1569. 2007. View Article : Google Scholar
25	Liu H, Tabuchi T, Takemura A, et al: The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression. Mol Med Rep. 1:699–704. 2008.PubMed/NCBI
26	Ietomi K: A study on the role of granulocytes in carcinoma-bearing hosts - G/L ratio as a new host indicator. Nippon Gan Chiryo Gakkai Shi. 25:662–671. 1990.(In Japanese).
27	Lee YS, Choi I, Ning Y, et al: Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis. Br J Cancer. 106:1833–1841. 2012. View Article : Google Scholar : PubMed/NCBI
28	Jung MY, Kim SH, Cho D and Kim TS: Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice. Oncol Rep. 22:1141–1147. 2009.PubMed/NCBI
29	Balkwill F and Mantovani A: Inflammation and cancer: back to Virchow? Lancet. 357:539–545. 2001. View Article : Google Scholar : PubMed/NCBI
30	Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD and Strieter RM: Inhibition of interleukin-8 reduces tumori-genesis of human non-small cell lung cancer in SCID mice. J Clin Invest. 97:2792–2802. 1996. View Article : Google Scholar : PubMed/NCBI
31	Ferrara N and Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev. 18:4–25. 1997. View Article : Google Scholar
32	Mizukami Y, Jo WS, Duerr EM, et al: Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med. 11:992–997. 2005.PubMed/NCBI