As a new member of the CD4+ effector T-cell family, T-helper 17 (Th17) cells, have emerged as an important mediator in inflammatory and autoimmune diseases. Th17 cells preferentially produce interleukin (IL)-17A, IL-17F, IL-21, IL-22, and IL-26 in humans. Recent studies suggest a potential role for Th17 cells in tumour development. The current study was designed to investigate the possible involvement of Th17 cells in the brain tumour medulloblastoma. Compared with 17 healthy volunteers, 23 patients with medulloblastoma had a higher proportion of Th17 cells in their peripheral blood. Increased populations of Th17 cells were also present in medulloblastoma-infiltrating T-cells. Furthermore, the mRNA levels for Th17-related factors (IL-17, IL-23 and retinoid orphan nuclear receptor) in tumour tissues and the serum concentrations of IL-17 and IL-23 protein were significantly increased in patients with medulloblastoma. The results indicate that Th17 cells may contribute to medulloblastoma pathogenesis.
RossiACaraccioloVRussoG: Medulloblastoma: From molecular pathology to therapy. Clin Cancer Res2008; 14: 971–976.
2.
CrawfordJRMacDonaldTJPackerRJ: Medulloblastoma in childhood: New biological advances. Lancet Neurol2007; 6: 1073–1085.
3.
ZeltzerPMBoyettJMFinlayJL: Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol1999; 17: 832–845.
4.
HarringtonLEHattonRDManganPR: Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol2005; 6: 1123–1132.
5.
BettelliECarrierYGaoW: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature2006; 441: 235–238.
6.
ManganPRHarringtonLEO'QuinnDB: Transforming growth factor-β induces development of the TH17 lineage. Nature2006; 441: 231–234.
7.
DongC: Diversification of T-helper-cell lineages: Finding the family root of IL-17-producing cells. Nat Rev Immunol2006; 6: 329–333.
8.
OuyangWKollsJKZhengY: The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity2008; 28: 454–467.
9.
DongC: TH17 cells in development: An updated view of their molecular identity and genetic programming. Nat Rev Immunol2008; 8: 337–348.
10.
IvanovIIMcKenzieBSZhouL: The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+T helper cells. Cell2006; 126: 1121–1133.
11.
McGeachyMJCuaDJ: Th17 cell differentiation: The long and winding road. Immunity2008; 28: 445–453.
12.
YangLAndersonDEBaecher-AllanC: IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature2008; 454: 350–352.
13.
VolpeEServantNZollingerR: A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses. Nat Immunol2008; 9: 650–657.
14.
ManelNUnutmazDLittmanDR: The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nat Immunol2008; 9: 641–649.
15.
KatoTFurumotoHOguraT: Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun2001; 282: 735–738.
16.
SteinerGENewmanMEPaiklD: Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate2003; 56: 171–182.
17.
CiréeAMichelLCamilleri-BröetS: Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). Int J Cancer2004; 112: 113–120.
18.
LangowskiJLZhangXWuL: IL-23 promotes tumour incidence and growth. Nature2006; 442: 461–465.
19.
Le GouvelloSBastuji-GarinSAloulouN: High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut2008; 57: 772–779.
20.
KryczekIWeiSZouL: Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol2007; 178: 6730–6733.
21.
MuranskiPBoniAAntonyPA: Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood2008; 112: 362–373.
SfanosKSBrunoTCMarisCH: Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res2008; 14: 3254–3261.
24.
WillisSNMallozziSSRodigSJ: The microenvironment of germ cell tumors harbors a prominent antigen-driven humoral response. J Immunol2009; 182: 3310–3317.
25.
RaffaghelloLNozzaPMorandiF: Expression and functional analysis of human leukocyte antigen class I antigen-processing machinery in medulloblastoma. Cancer Res2007; 67: 5471–5478.
26.
NumasakiMFukushiJOnoM: Interleukin-17 promotes angiogenesis and tumor growth. Blood2003; 101: 2620–2627.
27.
NumasakiMWatanabeMSuzukiT: 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 Immunol2005; 175: 6177–6189.
28.
AhmedNRatnayakeMSavoldoB: Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Cancer Res2007; 67: 5957–5964.
29.
WangJPham-MitchellNSchindlerC: Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-α-stimulated STAT2-independent production of IFN-γ in the brain. J Clin Invest2003; 112: 535–543.
