Recruitment and significance of Th22 cells and Th17 cells in malignant ascites

Yang,Xian‑Wen; Jiang,Hai‑Xing; Lei,Ronge; Lu,Wei‑Shun; Tan,Shi‑Hui; Qin,Shan‑Yu

doi:10.3892/ol.2018.9316

Recruitment and significance of Th22 cells and Th17 cells in malignant ascites

Authors:
- Xian‑Wen Yang
- Hai‑Xing Jiang
- Ronge Lei
- Wei‑Shun Lu
- Shi‑Hui Tan
- Shan‑Yu Qin
View Affiliations

Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: August 16, 2018 https://doi.org/10.3892/ol.2018.9316
Pages: 5389-5397

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

T helper (Th)22 and Th17 cells are implicated in the pathogenesis of a number of types of cancer. However, the function of Th22 and Th17 cells in malignant ascites (MA) remains unknown. The present study aimed at examining the distribution, phenotypes, recruitment, and prognostic value of Th22 and Th17 cells in MA from patients with hepatocellular carcinoma (HCC). A total of 26 patients with HCC with MA and 15 healthy controls were included in the present study. The proportion of Th22 cells, Th17 cells, C‑C motif chemokine receptor (CCR)4, CCR6 and CCR10 were examined using flow cytometry. Interleukin (IL‑)22, IL‑17, C‑C motif chemokine ligand (CCL)20, CCL22 and CCL27 were investigated using ELISA. In addition, the chemoattractant activity of chemokines for Th22 and Th17 cells in vitro were examined via a chemotaxis assay. The results of the present study demonstrated that Th22 cells, Th17 cells, IL‑22 and IL‑17 were significantly increased in MA compared with the corresponding blood and peripheral blood from healthy controls. Additionally, Th22 cells expressed increased concentrations of CCR6, CCR4 and CCR10, and Th17 cells expressed increased concentrations of CCR4 and CCR6 in MA compared with the corresponding blood. The chemotaxis assay revealed that CCL20/CCR6, CCL22/CCR4 and CCL27/CCR10 were responsible for the recruitment of Th22 cells into MA, whereas CCL22/CCR4 was responsible for the recruitment of Th17 cells. Furthermore, the patients with an increased number of Th17 cells exhibited an increased survival time compared with patients with a limited number of Th17 cells. Th22 and Th17 cells serve an important function in the development of MA, and the accumulation of Th22 and Th17 cells in MA may be due to a local increase in proinflammatory cytokines and chemokines. Increased Th17 cell numbers in MA may indicate the improvement of patient survival.

View Figures

View References

1	Smith EM and Jayson GC: The current and future management of malignant ascites. Clin Oncol (R Coll Radiol). 15:59–72. 2003. View Article : Google Scholar : PubMed/NCBI
2	Adam RA and Adam YG: Malignant ascites: Past, present, and future. J Am Coll Surg. 198:999–1011. 2004. View Article : Google Scholar : PubMed/NCBI
3	Hao C, Shi Y, Yu J, Wei X, Li S and Tong Z: The therapeutic function of the chemokine RANTES on the H22 hepatoma ascites model. Mol Cell Biochem. 367:93–102. 2012. View Article : Google Scholar : PubMed/NCBI
4	Zhang N, Pan HF and Ye DQ: Th22 in inflammatory and autoimmune disease: Prospects for therapeutic intervention. Mol Cell Biochem. 353:41–46. 2011. View Article : Google Scholar : PubMed/NCBI
5	Eyerich K, Pennino D, Scarponi C, Foerster S, Nasorri F, Behrendt H, Ring J, Traidl-Hoffmann C, Albanesi C and Cavani A: IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol. 123:59–66.e4. 2009. View Article : Google Scholar : PubMed/NCBI
6	Dumoutier L, Louahed J and Renauld JC: Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 164:1814–1819. 2000. View Article : Google Scholar : PubMed/NCBI
7	Qin S, Ma S, Huang X, Lu D, Zhou Y and Jiang H: Th22 cells are associated with hepatocellular carcinoma development and progression. Chin J Cancer Res. 26:135–141. 2014.PubMed/NCBI
8	Zhang W, Chen Y, Wei H, Zheng C, Sun R, Zhang J and Tian Z: Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. Clin Cancer Res. 14:6432–6439. 2008. View Article : Google Scholar : PubMed/NCBI
9	Bettelli E, Korn T, Oukka M and Kuchroo VK: Induction and effector functions of T(H)17 cells. Nature. 453:1051–1057. 2008. View Article : Google Scholar : PubMed/NCBI
10	Bettelli E, Korn T and Kuchroo VK: Th17: The third member of the effector T cell trilogy. Curr Opin Immunol. 19:652–657. 2007. View Article : Google Scholar : PubMed/NCBI
11	Guéry L and Hugues S: Th17 cell plasticity and functions in cancer immunity. Biomed Res Int. 2015:3146202015. View Article : Google Scholar : PubMed/NCBI
12	Ye ZJ, Zhou Q, Gu YY, Qin SM, Ma WL, Xin JB, Tao XN and Shi HZ: Generation and differentiation of IL-17-producing CD4+ T cells in malignant pleural effusion. J Immunol. 185:6348–6354. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ye ZJ, Zhou Q, Yuan ML, Du RH, Yang WB, Xiong XZ, Huang B and Shi HZ: Differentiation and recruitment of IL-22-producing helper T cells stimulated by pleural mesothelial cells in tuberculous pleurisy. Am J Respir Crit Care Med. 185:660–669. 2012. View Article : Google Scholar : PubMed/NCBI
14	Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B and Prat A: Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 13:1173–1175. 2007. View Article : Google Scholar : PubMed/NCBI
15	You QH, Sun GY, Wang N, Shen JL and Wang Y: Interleukin-17F-induced pulmonary microvascular endothelial monolayer hyperpermeability via the protein kinase C pathway. J Surg Res. 162:110–121. 2010. View Article : Google Scholar : PubMed/NCBI
16	Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M and Fouser LA: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 203:2271–2279. 2006. View Article : Google Scholar : PubMed/NCBI
17	Volpe E, Touzot M, Servant N, Marloie-Provost MA, Hupé P, Barillot E and Soumelis V: Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production. Blood. 114:3610–3614. 2009. View Article : Google Scholar : PubMed/NCBI
18	Ye ZJ, Xu LL, Zhou Q, Cui A, Wang XJ, Zhai K, Wang Z, Tong ZH and Shi HZ: Recruitment of IL-27-producing CD4(+) T cells and effect of IL-27 on pleural mesothelial cells in tuberculous pleurisy. Lung. 193:539–548. 2015. View Article : Google Scholar : PubMed/NCBI
19	Trifari S, Kaplan CD, Tran EH, Crellin NK and Spits H: Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 10:864–871. 2009. View Article : Google Scholar : PubMed/NCBI
20	Duhen T, Geiger R, Jarrossay D, Lanzavecchia A and Sallusto F: Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol. 10:857–863. 2009. View Article : Google Scholar : PubMed/NCBI
21	Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J and Ouyang W: Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 445:648–651. 2007. View Article : Google Scholar : PubMed/NCBI
22	Nishihara M, Ogura H, Ueda N, Tsuruoka M, Kitabayashi C, Tsuji F, Aono H, Ishihara K, Huseby E, Betz UA, et al: IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state. Int Immunol. 19:695–702. 2007. View Article : Google Scholar : PubMed/NCBI
23	Moser B and Loetscher P: Lymphocyte traffic control by chemokines. Nat Immunol. 2:123–128. 2001. View Article : Google Scholar : PubMed/NCBI
24	Xiao C, Zhou Q, Li X, Li H, Meng T, Zhong Y, Pu J, Zhu M, Xu Y, Gan L, et al: Differentiation and recruitment of IL-22-producing helper T cells in lgA nephropathy. Am J Transl Res. 8:3872–3882. 2016.PubMed/NCBI
25	Bu XN, Zhou Q, Zhang JC, Ye ZJ, Tong ZH and Shi HZ: Recruitment and phenotypic characteristics of interleukin 9-producing CD4+ T cells in malignant pleural effusion. Lung. 191:385–389. 2013. View Article : Google Scholar : PubMed/NCBI
26	Liao R, Sun J, Wu H, Yi Y, Wang JX, He HW, Cai XY, Zhou J, Cheng YF, Fan J and Qiu SJ: High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. J Exp Clin Cancer Res. 32:32013. View Article : Google Scholar : PubMed/NCBI
27	Punt S, Langenhoff JM, Putter H, Fleuren GJ, Gorter A and Jordanova ES: The correlations between IL-17 vs. Th17 cells and cancer patient survival: A systematic review. Oncoimmunology. 4:e9845472015. View Article : Google Scholar : PubMed/NCBI
28	Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW and Dong C: T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 31:787–798. 2009. View Article : Google Scholar : PubMed/NCBI
29	Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, et al: Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 114:1141–1149. 2009. View Article : Google Scholar : PubMed/NCBI
30	Jia L and Wu C: The biology and functions of Th22 cells. Adv Exp Med Biol. 841:209–230. 2014. View Article : Google Scholar : PubMed/NCBI
31	Niccolai E, Taddei A, Ricci F, Rolla S, D'Elios MM, Benagiano M, Bechi P, Bencini L, Ringressi MN, Pini A, et al: Intra-tumoral IFN-γ-producing Th22 cells correlate with TNM staging and the worst outcomes in pancreatic cancer. Clin Sci (Lond). 130:247–258. 2016. View Article : Google Scholar : PubMed/NCBI
32	Di Lullo G, Marcatti M, Heltai S, Brunetto E, Tresoldi C, Bondanza A, Bonini C, Ponzoni M, Tonon G, Ciceri F, et al: Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival. Oncoimmunology. 4:e10054602015. View Article : Google Scholar : PubMed/NCBI
33	Huang YH, Cao YF, Jiang ZY, Zhang S and Gao F: Th22 cell accumulation is associated with colorectal cancer development. World J Gastroenterol. 21:4216–4224. 2015. View Article : Google Scholar : PubMed/NCBI
34	Ling L, Zhao P, Yan G, Chen M, Zhang T, Wang L and Jiang Y: The frequency of Th17 and Th22 cells in patients with colorectal cancer at pre-operation and post-operation. Immunol Invest. 44:56–69. 2015. View Article : Google Scholar : PubMed/NCBI