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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways

Authors: Yi-Lan Zhang, Jiang Li, Hao-Yuan Mo, Fang Qiu, Li-Min Zheng, Chao-Nan Qian, Yi-Xin Zeng

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Increasing amounts of evidence indicate that tumor infiltrating lymphocytes (TIL) are correlated with the prognosis of cancer patients. This study focuses on the association between the densities of tumor infiltrating cytotoxic T lymphocytes (CTL), activated CTL, regulatory T lymphocytes (Treg) and Th17 lymphocytes, and the prognosis and clinicopathological features of nasopharyngeal carcinoma (NPC) patients.

Results

Double immunohistochemical staining was performed in 106 biopsy specimens from newly diagnosed NPC patients. Prognostic values of infiltrating lymphocyte densities were evaluated by Kaplan-Meier analysis and Cox regression. The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05). For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01). Meanwhile a low density of CD8+TIL or high ratio of FOXP3+TIL to CD8+TIL was correlated with better PFS in early stage patients (Stages I and II, P < 0.05). No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

Conclusions

Our study identifies for the first time the tumor infiltrating Foxp3+ TIL as an independent favorable factor in the prognosis of NPC patients, especially for the patients with late-stage diseases.
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Literature
1.
Guigay J, Temam S, Bourhis J, Pignon JP, Armand JP: Nasopharyngeal carcinoma and therapeutic management: the place of chemotherapy. Ann Oncol. 2006, 17 (Suppl 10): x304-307. 10.1093/annonc/mdl278CrossRefPubMed
2.
Ma BB, Chan AT: Recent perspectives in the role of chemotherapy in the management of advanced nasopharyngeal carcinoma. Cancer. 2005, 103: 22-31. 10.1002/cncr.20768CrossRefPubMed
3.
Sanguineti G, Bossi P, Pou A, Licitra L: Timing of chemoradiotherapy and patient selection for locally advanced nasopharyngeal carcinoma. Clin Oncol (R Coll Radiol). 2003, 15: 451-460.CrossRef
4.
Ayyoub M, Deknuydt F, Raimbaud I, Dousset C, Leveque L, Bioley G, Valmori D: Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t. Proc Natl Acad Sci USA. 2009, 106: 8635-8640. 10.1073/pnas.0900621106PubMedCentralCrossRefPubMed
5.
Wei WI, Sham JS: Nasopharyngeal carcinoma. Lancet. 2005, 365: 2041-2054. 10.1016/S0140-6736(05)66698-6CrossRefPubMed
6.
Young LS, Rickinson AB: Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004, 4: 757-768. 10.1038/nrc1452CrossRefPubMed
7.
8.
Zeng YX, Jia WH: Familial nasopharyngeal carcinoma. Semin Cancer Biol. 2002, 12: 443-450. 10.1016/S1044579X02000871CrossRefPubMed
9.
Lakhdar M, Ben Aribia MH, Maalej M, Ladgham A: Selective homing of phenotypically lytic cells within nasopharyngeal carcinoma biopsies: numerous CD8- and CD16-positive cells in the tumor. Int J Cancer. 1991, 48: 57-61.CrossRefPubMed
10.
Ruffini E, Asioli S, Filosso PL, Lyberis P, Bruna MC, Macri L, Daniele L, Oliaro A: Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ann Thorac Surg. 2009, 87: 365-371. discussion 371-362., 10.1016/j.athoracsur.2008.10.067CrossRefPubMed
11.
Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, ten Hoor KA, Hollema H, Boezen HM, Zee van der AG, Daemen T, Nijman HW: Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009, 58: 449-459. 10.1007/s00262-008-0583-5CrossRefPubMed
12.
Tomsova M, Melichar B, Sedlakova I, Steiner I: Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol. 2008, 108: 415-420. 10.1016/j.ygyno.2007.10.016CrossRefPubMed
13.
Dunn GP, Dunn IF, Curry WT: Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007, 7: 12-PubMedCentralPubMed
14.
Couzin J: Cancer. T cells a boon for colon cancer prognosis. Science. 2006, 313: 1868-1869. 10.1126/science.313.5795.1868bCrossRefPubMed
15.
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K: Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005, 102: 18538-18543. 10.1073/pnas.0509182102PubMedCentralCrossRefPubMed
16.
Prall F, Duhrkop T, Weirich V, Ostwald C, Lenz P, Nizze H, Barten M: Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability. Hum Pathol. 2004, 35: 808-816. 10.1016/j.humpath.2004.01.022CrossRefPubMed
17.
Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Itoh T, Morikawa T, Okushiba S, Kondo S, Katoh H: CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas. 2004, 28: e26-31. 10.1097/00006676-200401000-00023CrossRefPubMed
18.
Sobhani I, Le Gouvello S: Critical role for CD8+FoxP3+ regulatory T cells in colon cancer immune response in humans. Gut. 2009, 58: 743-744. 10.1136/gut.2008.175521CrossRefPubMed
19.
Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B: Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol. 2009, 27: 186-192. 10.1200/JCO.2008.18.7229CrossRefPubMed
20.
Gjerdrum LM, Woetmann A, Odum N, Burton CM, Rossen K, Skovgaard GL, Ryder LP, Ralfkiaer E: FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival. Leukemia. 2007, 21: 2512-2518. 10.1038/sj.leu.2404913CrossRefPubMed
21.
Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, Zhang Z, Yang H, Zhang H, Zhou C, Yao J, Jin L, Wang H, Yang Y, Fu YX, Wang FS: Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007, 132: 2328-2339. 10.1053/j.gastro.2007.03.102CrossRefPubMed
22.
Yu P, Fu YX: Tumor-infiltrating T lymphocytes: friends or foes?. Lab Invest. 2006, 86: 231-245. 10.1038/labinvest.3700389CrossRefPubMed
23.
Sasaki A, Tanaka F, Mimori K, Inoue H, Kai S, Shibata K, Ohta M, Kitano S, Mori M: Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma. Eur J Surg Oncol. 2008, 34: 173-179.CrossRefPubMed
24.
Yoshioka T, Miyamoto M, Cho Y, Ishikawa K, Tsuchikawa T, Kadoya M, Li L, Mishra R, Ichinokawa K, Shoji Y, Matsumura Y, Shichinohe T, Hirano S, Shinohara T, Itoh T, Kondo S: Infiltrating regulatory T cell numbers is not a factor to predict patient's survival in oesophageal squamous cell carcinoma. Br J Cancer. 2008, 98: 1258-1263. 10.1038/sj.bjc.6604294PubMedCentralCrossRefPubMed
25.
Lee NR, Song EK, Jang KY, Choi HN, Moon WS, Kwon K, Lee JH, Yim CY, Kwak JY: Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma. 2008, 49: 247-256. 10.1080/10428190701824536CrossRefPubMed
26.
Grabenbauer GG, Lahmer G, Distel L, Niedobitek G: Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res. 2006, 12: 3355-3360. 10.1158/1078-0432.CCR-05-2434CrossRefPubMed
27.
Gottschalk S, Bollard CM, Straathof KC, Louis CU, Savoldo B, Dotti G, Brenner MK, Heslop HE, Rooney CM: T cell therapies. Ernst Schering Found Symp Proc. 2006, 69-82.
28.
Chan AT, Teo PM, Huang DP: Pathogenesis and treatment of nasopharyngeal carcinoma. Semin Oncol. 2004, 31: 794-801. 10.1053/j.seminoncol.2004.09.008CrossRefPubMed
29.
Tzankov A, Meier C, Hirschmann P, Went P, Pileri SA, Dirnhofer S: Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma. Haematologica. 2008, 93: 193-200. 10.3324/haematol.11702CrossRefPubMed
30.
Carreras J, Lopez-Guillermo A, Fox BC, Colomo L, Martinez A, Roncador G, Montserrat E, Campo E, Banham AH: High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood. 2006, 108: 2957-2964. 10.1182/blood-2006-04-018218CrossRefPubMed
31.
Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C: The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005, 11: 8326-8331. 10.1158/1078-0432.CCR-05-1244CrossRefPubMed
32.
Bhairavabhotla RK, Verm V, Tongaonkar H, Shastri S, Dinshaw K, Chiplunkar S: Role of IL-10 in immune suppression in cervical cancer. Indian J Biochem Biophys. 2007, 44: 350-356.PubMed
33.
Visser J, Nijman HW, Hoogenboom BN, Jager P, van Baarle D, Schuuring E, Abdulahad W, Miedema F, Zee van der AG, Daemen T: Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia. Clin Exp Immunol. 2007, 150: 199-209.PubMedCentralCrossRefPubMed
34.
Molling JW, de Gruijl TD, Glim J, Moreno M, Rozendaal L, Meijer CJ, Eertwegh van den AJ, Scheper RJ, von Blomberg ME, Bontkes HJ: CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int J Cancer. 2007, 121: 1749-1755. 10.1002/ijc.22894CrossRefPubMed
35.
Lund JM, Hsing L, Pham TT, Rudensky AY: Coordination of early protective immunity to viral infection by regulatory T cells. Science. 2008, 320: 1220-1224. 10.1126/science.1155209PubMedCentralCrossRefPubMed
36.
Dougan M, Dranoff G: Immune therapy for cancer. Annu Rev Immunol. 2009, 27: 83-117. 10.1146/annurev.immunol.021908.132544CrossRefPubMed
37.
Curotto de Lafaille MA, Lafaille JJ: Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?. Immunity. 2009, 30: 626-635. 10.1016/j.immuni.2009.05.002CrossRefPubMed
38.
van Maren WW, Jacobs JF, de Vries IJ, Nierkens S, Adema GJ: Toll-like receptor signalling on Tregs: to suppress or not to suppress?. Immunology. 2008, 124: 445-452. 10.1111/j.1365-2567.2008.02871.xPubMedCentralCrossRefPubMed
39.
40.
41.
Barnett BG, Ruter J, Kryczek I, Brumlik MJ, Cheng PJ, Daniel BJ, Coukos G, Zou W, Curiel TJ: Regulatory T cells: a new frontier in cancer immunotherapy. Adv Exp Med Biol. 2008, 622: 255-260.CrossRefPubMed
42.
Wang HY, Wang RF: Regulatory T cells and cancer. Curr Opin Immunol. 2007, 19: 217-223. 10.1016/j.coi.2007.02.004CrossRefPubMed
43.
Zhou X, Bailey-Bucktrout S, Jeker LT, Bluestone JA: Plasticity of CD4(+) FoxP3(+) T cells. Curr Opin Immunol. 2009, 21: 281-285. 10.1016/j.coi.2009.05.007PubMedCentralCrossRefPubMed
44.
Zhou L, Chong MM, Littman DR: Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009, 30: 646-655. 10.1016/j.immuni.2009.05.001CrossRefPubMed
45.
Wang HY, Peng G, Guo Z, Shevach EM, Wang RF: Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J Immunol. 2005, 174: 2661-2670.CrossRefPubMed
46.
Li J, Zeng XH, Mo HY, Rolen U, Gao YF, Zhang XS, Chen QY, Zhang L, Zeng MS, Li MZ, Huang WL, Wang XN, Zeng YX, Masucci MG: Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy. PLoS One. 2007, 2: e1122- 10.1371/journal.pone.0001122PubMedCentralCrossRefPubMed
47.
Oudejans JJ, Harijadi H, Kummer JA, Tan IB, Bloemena E, Middeldorp JM, Bladergroen B, Dukers DF, Vos W, Meijer CJ: High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent. J Pathol. 2002, 198: 468-475. 10.1002/path.1236CrossRefPubMed
48.
Yip WK, Abdullah MA, Yusoff SM, Seow HF: Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced zeta-chain expression in nasopharyngeal carcinoma patients. Clin Exp Immunol. 2009, 155: 412-422. 10.1111/j.1365-2249.2008.03793.xPubMedCentralCrossRefPubMed
49.
Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ: Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007, 27: 635-646. 10.1016/j.immuni.2007.08.014CrossRefPubMed
50.
von Boehmer H: Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005, 6: 338-344. 10.1038/ni1180CrossRefPubMed
51.
Yang J, Chu Y, Yang X, Gao D, Zhu L, Wan L, Li M: Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009, 60: 1472-1483. 10.1002/art.24499CrossRefPubMed
52.
Mihara M, Ohsugi Y, Kishimoto T: Evidence for the role of Th17 cell inhibition in the prevention of autoimmune diseases by anti-interluekin-6 receptor antibody. Biofactors. 2009, 35: 47-51. 10.1002/biof.9CrossRefPubMed
53.
54.
Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM: Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 2006, 24: 677-688. 10.1016/j.immuni.2006.06.002CrossRefPubMed
55.
Voo KS, Wang YH, Santori FR, Boggiano C, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ: Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA. 2009, 106: 4793-4798. 10.1073/pnas.0900408106PubMedCentralCrossRefPubMed
56.
Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W: Phenotype, distribution, generation, functional and clinical relevance of Th17 cells in the human tumor environments. Blood. 2009, 114 (6): 1141-9. 10.1182/blood-2009-03-208249PubMedCentralCrossRefPubMed
57.
Chan AT, Felip E: Nasopharyngeal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008, 19 (Suppl 2): ii81-82. 10.1093/annonc/mdn098PubMed
Metadata
Title
Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways
Authors
Yi-Lan Zhang
Jiang Li
Hao-Yuan Mo
Fang Qiu
Li-Min Zheng
Chao-Nan Qian
Yi-Xin Zeng
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-4

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