Research progress on the relationship between T helper cell 17, interleukin-17 and lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIN Feng ^1,2 ,  LIU Lunxu ^1,2

1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. West China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Chengdu, 610041, P.R.China;

Corresponding author：

LIU Lunxu, Email: lunxu_liu@aliyun.com

Keywords：

T helper cell 17; interleukin-17; lung cancer; inflammatory factors; signaling pathway

DOI：

10.7507/1007-4848.201803038

Video：

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Abstract Full text Figures/Tables Video References Cited by

A new independent subtype CD4⁺ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.

Citation： LIN Feng, LIU Lunxu. Research progress on the relationship between T helper cell 17, interleukin-17 and lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(1): 92-96. doi: 10.7507/1007-4848.201803038 Copy

1.	Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006, 441(7090): 235-238.
2.	Mangan PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature, 2006, 441(7090): 231-234.
3.	Veldhoen M, Hocking RJ, Atkins CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 2006, 24(2): 179-189.
4.	Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol, 2008, 9(6): 641-649.
5.	Yang L, Anderson DE, Baecher-Allan C, et al. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature, 2008, 454(7202): 350-352.
6.	Liang SC, Tan XY, Luxenberg DP, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med, 2006, 203(10): 2271-2279.
7.	Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol, 2009, 9(8): 556-567.
8.	Zhang X, Angkasekwinai P, Dong C, et al. Structure and function of interleukin-17 family cytokines. Protein Cell, 2011, 2(1): 26-40.
9.	Toy D, Kugler D, Wolfson M, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol, 2006, 177(1): 36-39.
10.	Iwakura Y, Ishigame H, Saijo S, et al. Functional specialization of interleukin-17 family members. Immunity, 2011, 34(2): 149-162.
11.	Fossiez F, Djossou O, Chomarat P, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med, 1996, 183(6): 2593-2603.
12.	Moseley TA, Haudenschild DR, Rose L, et al. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev, 2003, 14(2): 155-174.
13.	Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol, 2010, 10(7): 479-489.
14.	Kolls JK, Lindén A. Interleukin-17 family members and inflammation. Immunity, 2004, 21(4): 467-476.
15.	Shen F, Gaffen SL. Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine, 2008, 41(2): 92-104.
16.	Gaffen SL. An overview of IL-17 function and signaling. Cytokine, 2008, 43(3): 402-407.
17.	Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology, 2010, 129(3): 311-321.
18.	Tartour E, Fossiez F, Joyeux I, et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res, 1999, 59(15): 3698-3704.
19.	Kato T, Furumoto H, Ogura T, et al. Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun, 2001, 282(3): 735-738.
20.	Numasaki M, Fukushi J, Ono M, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood, 2003, 101(7): 2620-2627.
21.	Numasaki M, Watanabe M, Suzuki T, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol, 2005, 175(9): 6177-6189.
22.	Liu L, Ge D, Ma L, et al. Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. J Thorac Oncol, 2012, 7(7): 1091-1100.
23.	Qian Y, Liu C, Hartupee J, et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol, 2007, 8(3): 247-256.
24.	Liu C, Qian W, Qian Y, et al. Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci Signal, 2009, 2(92): ra63.
25.	Qu F, Gao H, Zhu S, et al. TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation. Mol Cell Biol, 2012, 32(19): 3925-3937.
26.	Gu K, Li MM, Shen J, et al. Interleukin-17-induced EMT promotes lung cancer cell migration and invasion via NF-κB/ZEB1 signal pathway. Am J Cancer Res, 2015, 5(3): 1169-1179.
27.	Roussel L, Houle F, Chan C, et al. IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J Immunol, 2010, 184(8): 4531-4537.
28.	Martel-Pelletier J, Mineau F, Jovanovic D, et al. Mitogen-activated protein kinase and nuclear factor kappaB together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated proten kinase (MAPKAPK). Arthritis Rheum, 1999, 42(11): 2399-2409.
29.	Aronheim A, Engelberg D, Li N, et al. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell, 1994, 78(6): 949-961.
30.	Jelinek T, Catling AD, Reuter CW, et al. RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol Cell Biol, 1994, 14(12): 8212-8218.
31.	Chen X, Wan J, Liu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer, 2010, 69(3): 348-354.
32.	Chen X, Xie Q, Cheng X, et al. Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer: Enhanced production of vascular endothelial growth factor C in non-small-cell lung carcinoma cells. Cancer Sci, 2010, 101(11): 2384-2390.
33.	Wang L, Yi T, Kortylewski M, et al. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med, 2009, 206(7): 1457-1464.
34.	Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol, 2007, 7(1): 41-51.
35.	Zhang X, Yue P, Page BD, et al. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc Natl Acad Sci USA, 2012, 109(24): 9623-9628.
36.	Lavecchia A, Di Giovanni C, Novellino E. STAT-3 inhibitors: state of the art and new horizons for cancer treatment. Curr Med Chem, 2011, 18(16): 2359-2375.
37.	Zhao B, Meng LQ, Huang HN, et al. A novel functional polymorphism, 16974 A/C, in the interleukin-12-3' untranslated region is associated with risk of glioma. DNA Cell Biol, 2009, 28(7): 335-341.
38.	Cheng S, Shao Z, Liu X, et al. Interleukin 17A polymorphism elevates gene expression and is associated with increased risk of nonsmall cell lung cancer. DNA Cell Biol, 2015, 34(1): 63-68.
39.	Morath R, Klein T, Seyberth HW, et al. Immunolocalization of the four prostaglandin E2 receptor proteins EP1, EP2, EP3, and EP4 in human kidney. J Am Soc Nephrol, 1999, 10(9): 1851-1860.
40.	Witz IP, Levy-Nissenbaum O. The tumor microenvironment in the post-PAGET era. Cancer Lett, 2006, 242(1): 1-10.
41.	Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res, 2006, 66(2): 605-612.
42.	Ma J, Liu L, Che G, et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer, 2010, 10: 112.
43.	He G, Zhang B, Zhang B, et al. Th17 cells and IL-17 are increased in patients with brain metastases from the primary lung cancer. Zhongguo Fei Ai Za Zhi, 2013, 16(9): 476-481.
44.	Zhang X, Weng W, Xu W, et al. Prognostic significance of interleukin 17 in cancer: a meta-analysis. Int J Clin Exp Med, 2014, 7(10): 3258-3269.
45.	Xu C, Hao K, Yu L, et al. Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer. Biomarkers, 2014, 19(4): 287-290.
46.	Lin Q, Xue L, Tian T, et al. Prognostic value of serum IL-17 and VEGF levels in small cell lung cancer. Int J Biol Markers, 2015, 30(4): e359-e363.
47.	Shen N, Wang J, Zhao M, et al. Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice. Inhal Toxicol, 2011, 23(4): 212-218.
48.	Kim JH, Choi YJ, Lee BH, et al. Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells. J Allergy Clin Immunol, 2016, 137(5): 1466-1476.
49.	Solt LA, Kumar N, Nuhant P, et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature, 2011, 472(7344): 491-494.

1. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006, 441(7090): 235-238.
2. Mangan PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature, 2006, 441(7090): 231-234.
3. Veldhoen M, Hocking RJ, Atkins CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 2006, 24(2): 179-189.
4. Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol, 2008, 9(6): 641-649.
5. Yang L, Anderson DE, Baecher-Allan C, et al. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature, 2008, 454(7202): 350-352.
6. Liang SC, Tan XY, Luxenberg DP, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med, 2006, 203(10): 2271-2279.
7. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol, 2009, 9(8): 556-567.
8. Zhang X, Angkasekwinai P, Dong C, et al. Structure and function of interleukin-17 family cytokines. Protein Cell, 2011, 2(1): 26-40.
9. Toy D, Kugler D, Wolfson M, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol, 2006, 177(1): 36-39.
10. Iwakura Y, Ishigame H, Saijo S, et al. Functional specialization of interleukin-17 family members. Immunity, 2011, 34(2): 149-162.
11. Fossiez F, Djossou O, Chomarat P, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med, 1996, 183(6): 2593-2603.
12. Moseley TA, Haudenschild DR, Rose L, et al. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev, 2003, 14(2): 155-174.
13. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol, 2010, 10(7): 479-489.
14. Kolls JK, Lindén A. Interleukin-17 family members and inflammation. Immunity, 2004, 21(4): 467-476.
15. Shen F, Gaffen SL. Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine, 2008, 41(2): 92-104.
16. Gaffen SL. An overview of IL-17 function and signaling. Cytokine, 2008, 43(3): 402-407.
17. Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology, 2010, 129(3): 311-321.
18. Tartour E, Fossiez F, Joyeux I, et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res, 1999, 59(15): 3698-3704.
19. Kato T, Furumoto H, Ogura T, et al. Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun, 2001, 282(3): 735-738.
20. Numasaki M, Fukushi J, Ono M, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood, 2003, 101(7): 2620-2627.
21. Numasaki M, Watanabe M, Suzuki T, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol, 2005, 175(9): 6177-6189.
22. Liu L, Ge D, Ma L, et al. Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. J Thorac Oncol, 2012, 7(7): 1091-1100.
23. Qian Y, Liu C, Hartupee J, et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol, 2007, 8(3): 247-256.
24. Liu C, Qian W, Qian Y, et al. Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci Signal, 2009, 2(92): ra63.
25. Qu F, Gao H, Zhu S, et al. TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation. Mol Cell Biol, 2012, 32(19): 3925-3937.
26. Gu K, Li MM, Shen J, et al. Interleukin-17-induced EMT promotes lung cancer cell migration and invasion via NF-κB/ZEB1 signal pathway. Am J Cancer Res, 2015, 5(3): 1169-1179.
27. Roussel L, Houle F, Chan C, et al. IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J Immunol, 2010, 184(8): 4531-4537.
28. Martel-Pelletier J, Mineau F, Jovanovic D, et al. Mitogen-activated protein kinase and nuclear factor kappaB together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated proten kinase (MAPKAPK). Arthritis Rheum, 1999, 42(11): 2399-2409.
29. Aronheim A, Engelberg D, Li N, et al. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell, 1994, 78(6): 949-961.
30. Jelinek T, Catling AD, Reuter CW, et al. RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol Cell Biol, 1994, 14(12): 8212-8218.
31. Chen X, Wan J, Liu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer, 2010, 69(3): 348-354.
32. Chen X, Xie Q, Cheng X, et al. Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer: Enhanced production of vascular endothelial growth factor C in non-small-cell lung carcinoma cells. Cancer Sci, 2010, 101(11): 2384-2390.
33. Wang L, Yi T, Kortylewski M, et al. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med, 2009, 206(7): 1457-1464.
34. Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol, 2007, 7(1): 41-51.
35. Zhang X, Yue P, Page BD, et al. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc Natl Acad Sci USA, 2012, 109(24): 9623-9628.
36. Lavecchia A, Di Giovanni C, Novellino E. STAT-3 inhibitors: state of the art and new horizons for cancer treatment. Curr Med Chem, 2011, 18(16): 2359-2375.
37. Zhao B, Meng LQ, Huang HN, et al. A novel functional polymorphism, 16974 A/C, in the interleukin-12-3' untranslated region is associated with risk of glioma. DNA Cell Biol, 2009, 28(7): 335-341.
38. Cheng S, Shao Z, Liu X, et al. Interleukin 17A polymorphism elevates gene expression and is associated with increased risk of nonsmall cell lung cancer. DNA Cell Biol, 2015, 34(1): 63-68.
39. Morath R, Klein T, Seyberth HW, et al. Immunolocalization of the four prostaglandin E2 receptor proteins EP1, EP2, EP3, and EP4 in human kidney. J Am Soc Nephrol, 1999, 10(9): 1851-1860.
40. Witz IP, Levy-Nissenbaum O. The tumor microenvironment in the post-PAGET era. Cancer Lett, 2006, 242(1): 1-10.
41. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res, 2006, 66(2): 605-612.
42. Ma J, Liu L, Che G, et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer, 2010, 10: 112.
43. He G, Zhang B, Zhang B, et al. Th17 cells and IL-17 are increased in patients with brain metastases from the primary lung cancer. Zhongguo Fei Ai Za Zhi, 2013, 16(9): 476-481.
44. Zhang X, Weng W, Xu W, et al. Prognostic significance of interleukin 17 in cancer: a meta-analysis. Int J Clin Exp Med, 2014, 7(10): 3258-3269.
45. Xu C, Hao K, Yu L, et al. Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer. Biomarkers, 2014, 19(4): 287-290.
46. Lin Q, Xue L, Tian T, et al. Prognostic value of serum IL-17 and VEGF levels in small cell lung cancer. Int J Biol Markers, 2015, 30(4): e359-e363.
47. Shen N, Wang J, Zhao M, et al. Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice. Inhal Toxicol, 2011, 23(4): 212-218.
48. Kim JH, Choi YJ, Lee BH, et al. Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells. J Allergy Clin Immunol, 2016, 137(5): 1466-1476.
49. Solt LA, Kumar N, Nuhant P, et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature, 2011, 472(7344): 491-494.

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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress on the relationship between T helper cell 17, interleukin-17 and lung cancer

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