Skip to main content

Advertisement

SpringerLink
Log in

Colitis-associated cancer: the role of T cells in tumor development

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Chronic inflammation severely increases the risk for cancer development as seen in patients with inflammatory bowel disease (IBD). Although the exact mechanisms of inflammation-associated tumor development remain to be shown, a role for the adaptive immune system has been implicated in colitis-associated cancer (CAC). In fact, CD4+ effector T cells, which promote chronic inflammation in IBD, create a tumor convenient environment, which can lead to cancer initiation, promotion, and progression. Thereby, the cytokines interleukin-6 and tumor necrosis factor-α constitute an important link between inflammation and tumor growth. Furthermore, cytotoxic CD8+ T cells, which usually are protective as part of the host antitumor immune response in sporadic cancer, can contribute to the aggravation of chronic inflammation and thereby support tumor development. In contrast, regulatory T cells, which have been shown to attenuate tumor immunosurveillance, act as potent suppressors of chronic inflammation and thus can have protective effects in CAC. This review discusses the role of the adaptive immune response and especially T cells in the pathogenesis CAC and possible implications for the therapeutic applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gyde S, Prior P, Dew MJ, Saunders V, Waterhouse JA, Allan RN (1982) Mortality in ulcerative colitis. Gastroenterology 83:36–43

    CAS  PubMed  Google Scholar 

  2. Choi PM, Zelig MP (1994) Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 35:950–954. doi:10.1136/gut.35.7.950

    Article  CAS  PubMed  Google Scholar 

  3. Bernstein CN, Blanchard JF, Kliewer E, Wajda A (2001) Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91:854–862. doi:10.1002/1097-0142(20010215) 91:4<854::AID-CNCR1073>3.0.CO;2-Z

    Article  CAS  PubMed  Google Scholar 

  4. Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535. doi:10.1136/gut.48.4.526

    Article  CAS  PubMed  Google Scholar 

  5. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640. doi:10.1016/S0140-6736(07)60750-8

    Article  CAS  PubMed  Google Scholar 

  6. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434. doi:10.1038/nature06005

    Article  CAS  PubMed  Google Scholar 

  7. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429. doi:10.1056/NEJMra020831

    Article  CAS  PubMed  Google Scholar 

  8. Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA et al (1996) Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157:1261–1270

    CAS  PubMed  Google Scholar 

  9. Neurath MF (2007) IL-23: a master regulator in Crohn disease. Nat Med 13:26–28. doi:10.1038/nm0107-26

    Article  CAS  PubMed  Google Scholar 

  10. Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 14:433–439. doi:10.1016/j.semcancer.2004.06.006

    Article  CAS  PubMed  Google Scholar 

  11. Kundu JK, Surh YJ (2008) Inflammation: gearing the journey to cancer. Mutat Res 659:15–30. doi:10.1016/j.mrrev.2008.03.002

    Article  CAS  PubMed  Google Scholar 

  12. Roessner A, Kuester D, Malfertheiner P, Schneider-Stock R (2008) Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathol Res Pract 204:511–524. doi:10.1016/j.prp.2008.04.011

    Article  CAS  PubMed  Google Scholar 

  13. Wong M, Ziring D, Korin Y, Desai S, Kim SJ, Lin J et al (2008) TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol 126:121–136. doi:10.1016/j.clim.2007.08.013

    Article  CAS  PubMed  Google Scholar 

  14. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117:244–279. doi:10.1016/j.pharmthera.2007.10.001

    Article  CAS  PubMed  Google Scholar 

  15. Rutgeerts P, Vermeire S, Van Assche G (2009) Biological therapies for inflammatory bowel diseases. Gastroenterology 136:1182–1197. doi:10.1053/j.gastro.2009.02.001

    Article  CAS  PubMed  Google Scholar 

  16. Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S et al (2008) Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest 118:560–570. doi:10.1172/JCI32453

    CAS  PubMed  Google Scholar 

  17. Neurath MF, Pettersson S, Meyer Zum Büschenfelde KH, Strober W (1996) Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat Med 2:998–1004. doi:10.1038/nm0996-998

    Article  CAS  PubMed  Google Scholar 

  18. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ et al (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296. doi:10.1016/j.cell.2004.07.013

    Article  CAS  PubMed  Google Scholar 

  19. Atreya I, Atreya R, Neurath MF (2008) NF-kappaB in inflammatory bowel disease. J Intern Med 263:591–596. doi:10.1111/j.1365-2796.2008.01953.x

    Article  CAS  PubMed  Google Scholar 

  20. Mitsuyama K, Sasaki E, Toyonaga A, Ikeda H, Tsuruta O, Irie A et al (1991) Colonic mucosal interleukin-6 in inflammatory bowel disease. Digestion 50:104–111. doi:10.1159/000200747

    Article  CAS  PubMed  Google Scholar 

  21. Ito H, Takazoe M, Fukuda Y, Hibi T, Kusugami K, Andoh A et al (2004) A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 126:989–996. doi:10.1053/j.gastro.2004.01.012 discussion 947

    Article  CAS  PubMed  Google Scholar 

  22. Yamamoto M, Yoshizaki K, Kishimoto T, Ito H (2000) IL-6 is required for the development of Th1 cell-mediated murine colitis. J Immunol 164:4878–4882

    CAS  PubMed  Google Scholar 

  23. Rose-John S, Scheller J, Elson G, Jones SA (2006) Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol 80:227–236. doi:10.1189/jlb.1105674

    Article  CAS  PubMed  Google Scholar 

  24. Nishimoto N, Kishimoto T (2006) Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2:619–626. doi:10.1038/ncprheum0338

    Article  CAS  PubMed  Google Scholar 

  25. Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278. doi:10.1146/annurev.iy.08.040190.001345

    Article  PubMed  Google Scholar 

  26. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20. doi:10.1042/BJ20030407

    Article  CAS  PubMed  Google Scholar 

  27. Chung YC, Chang YF (2003) Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol 83:222–226. doi:10.1002/jso.10269

    Article  PubMed  Google Scholar 

  28. Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L et al (2002) Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol 102:169–178. doi:10.1006/clim.2001.5163

    Article  CAS  PubMed  Google Scholar 

  29. Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A et al (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:491–501. doi:10.1016/j.immuni.2004.07.020

    Article  CAS  PubMed  Google Scholar 

  30. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T et al (2009) gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15:91–102. doi:10.1016/j.ccr.2009.01.002

    Article  CAS  PubMed  Google Scholar 

  31. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S et al (2009) IL-6 and stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15:103–113. doi:10.1016/j.ccr.2009.01.001

    Article  CAS  PubMed  Google Scholar 

  32. Yu P, Fu YX (2006) Tumor-infiltrating T lymphocytes: friends or foes? Lab Invest 86:231–245. doi:10.1038/labinvest.3700389

    Article  CAS  PubMed  Google Scholar 

  33. Osawa E, Nakajima A, Fujisawa T, Kawamura YI, Toyama-Sorimachi N, Nakagama H et al (2006) Predominant T helper type 2-inflammatory responses promote murine colon cancers. Int J Cancer 118:2232–2236. doi:10.1002/ijc.21639

    Article  CAS  PubMed  Google Scholar 

  34. Strasly M, Cavallo F, Geuna M, Mitola S, Colombo MP, Forni G et al (2001) IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk. J Immunol 166:3890–3899

    CAS  PubMed  Google Scholar 

  35. Verbik DJ, Stinson WW, Brunda MJ, Kessinger A, Joshi SS (1996) In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma. Clin Exp Metastasis 14:219–229

    CAS  PubMed  Google Scholar 

  36. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M et al (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178:1223–1230. doi:10.1084/jem.178.4.1223

    Article  CAS  PubMed  Google Scholar 

  37. Nastala CL, Edington HD, McKinney TG, Tahara H, Nalesnik MA, Brunda MJ et al (1994) Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. J Immunol 153:1697–1706

    CAS  PubMed  Google Scholar 

  38. Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, Parmiani G et al (2007) Interleukin-12: biological properties and clinical application. Clin Cancer Res 13:4677–4685. doi:10.1158/1078-0432.CCR-07-0776

    Article  PubMed  Google Scholar 

  39. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998. doi:10.1038/ni1102-991

    Article  CAS  PubMed  Google Scholar 

  40. Shibata M, Nezu T, Kanou H, Abe H, Takekawa M, Fukuzawa M (2002) Decreased production of interleukin-12 and type 2 immune responses are marked in cachectic patients with colorectal and gastric cancer. J Clin Gastroenterol 34:416–420. doi:10.1097/00004836-200204000-00006

    Article  CAS  PubMed  Google Scholar 

  41. Kettunen HL, Kettunen AS, Rautonen NE (2003) Intestinal immune responses in wild-type and Apcmin/+ mouse, a model for colon cancer. Cancer Res 63:5136–5142

    CAS  PubMed  Google Scholar 

  42. Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666. doi:10.1056/NEJMoa051424

    Article  PubMed  Google Scholar 

  43. Endo Y, Marusawa H, Kou T, Nakase H, Fujii S, Fujimori T et al (2008) Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. Gastroenterology 135:889–898. doi:10.1053/j.gastro.2008.06.091 898.e881-883

    Article  CAS  PubMed  Google Scholar 

  44. Weedon DD, Shorter RG, Ilstrup DM, Huizenga KA, Taylor WF (1973) Crohn's disease and cancer. N Engl J Med 289:1099–1103

    CAS  PubMed  Google Scholar 

  45. Gyde SN, Prior P, Macartney JC, Thompson H, Waterhouse JA, Allan RN (1980) Malignancy in Crohn's disease. Gut 21:1024–1029. doi:10.1136/gut.21.12.1024

    Article  CAS  PubMed  Google Scholar 

  46. Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN (1994) Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 35:1590–1592. doi:10.1136/gut.35.11.1590

    Article  CAS  PubMed  Google Scholar 

  47. Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146. doi:10.1038/nri1001

    Article  CAS  PubMed  Google Scholar 

  48. Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F et al (1997) Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112:1169–1178. doi:10.1016/S0016-5085(97)70128-8

    Article  CAS  PubMed  Google Scholar 

  49. Stuber E, Strober W, Neurath M (1996) Blocking the CD40L–CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. J Exp Med 183:693–698. doi:10.1084/jem.183.2.693

    Article  CAS  PubMed  Google Scholar 

  50. Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182:1281–1290. doi:10.1084/jem.182.5.1281

    Article  CAS  PubMed  Google Scholar 

  51. Mannon PJ, Fuss IJ, Mayer L, Elson CO, Sandborn WJ, Present D et al (2004) Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med 351:2069–2079. doi:10.1056/NEJMoa033402

    Article  CAS  PubMed  Google Scholar 

  52. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B et al (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725. doi:10.1016/S1074-7613(00)00070-4

    Article  CAS  PubMed  Google Scholar 

  53. Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB et al (2007) Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132:2359–2370. doi:10.1053/j.gastro.2007.03.104

    Article  CAS  PubMed  Google Scholar 

  54. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463. doi:10.1126/science.1135245

    Article  CAS  PubMed  Google Scholar 

  55. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD et al (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240. doi:10.1084/jem.20041257

    Article  CAS  PubMed  Google Scholar 

  56. Fouser LA, Wright JF, Dunussi-Joannopoulos K, Collins M (2008) Th17 cytokines and their emerging roles in inflammation and autoimmunity. Immunol Rev 226:87–102. doi:10.1111/j.1600-065X.2008.00712.x

    Article  CAS  PubMed  Google Scholar 

  57. Fossiez F, Banchereau J, Murray R, Van Kooten C, Garrone P, Lebecque S (1998) Interleukin-17. Int Rev Immunol 16:541–551. doi:10.3109/08830189809043008

    Article  CAS  PubMed  Google Scholar 

  58. Korn T, Oukka M, Kuchroo V, Bettelli E (2007) Th17 cells: effector T cells with inflammatory properties. Semin Immunol 19:362–371. doi:10.1016/j.smim.2007.10.007

    Article  CAS  PubMed  Google Scholar 

  59. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B et al (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116:1310–1316. doi:10.1172/JCI21404

    Article  CAS  PubMed  Google Scholar 

  60. Leppkes M, Becker C, Ivanov II, Hirth S, Wirtz S, Neufert C et al (2008) RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology . doi:10.1053/j.gastro.2008.10.018

    PubMed  Google Scholar 

  61. Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C et al (2008) Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis 14:437–445. doi:10.1002/ibd.20339

    Article  PubMed  Google Scholar 

  62. Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K et al (2006) IL-23 promotes tumour incidence and growth. Nature 442:461–465. doi:10.1038/nature04808

    Article  CAS  PubMed  Google Scholar 

  63. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T et al (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101:2620–2627. doi:10.1182/blood-2002-05-1461

    Article  CAS  PubMed  Google Scholar 

  64. Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P (2000) Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 12:1092–1099. doi:10.1006/cyto.2000.0681

    Article  CAS  PubMed  Google Scholar 

  65. Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148. doi:10.1016/j.immuni.2004.07.017

    Article  CAS  PubMed  Google Scholar 

  66. Talmadge JE, Donkor M, Scholar E (2007) Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev 26:373–400. doi:10.1007/s10555-007-9072-0

    Article  PubMed  Google Scholar 

  67. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H et al (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491–3494

    CAS  PubMed  Google Scholar 

  68. Atreya I, Schimanski CC, Becker C, Wirtz S, Dornhoff H, Schnürer E et al (2007) The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer. Gut 56:1572–1578. doi:10.1136/gut.2006.117812

    Article  CAS  PubMed  Google Scholar 

  69. Smith CL, Dulphy N, Salio M, Cerundolo V (2002) Immunotherapy of colorectal cancer. Br Med Bull 64:181–200. doi:10.1093/bmb/64.1.181

    Article  CAS  PubMed  Google Scholar 

  70. Bergmann-Leitner ES, Duncan EH, Leitner WW (2003) Identification and targeting of tumor escape mechanisms: a new hope for cancer therapy? Curr Pharm Des 9:2009–2023. doi:10.2174/1381612033454199

    Article  CAS  PubMed  Google Scholar 

  71. Michael-Robinson JM, Pandeya N, Walsh MD, Biemer-Huttmann AE, Eri RD, Buttenshaw RL et al (2006) Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer. J Pathol 208:381–387. doi:10.1002/path.1895

    Article  CAS  PubMed  Google Scholar 

  72. Müller S, Lory J, Corazza N, Griffiths GM, Z'graggen K, Mazzucchelli L et al (1998) Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease. Am J Pathol 152:261–268

    PubMed  Google Scholar 

  73. Souza HS, Tortori CJ, Castelo-Branco MT, Carvalho AT, Margallo VS, Delgado CF et al (2005) Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways. Int J Colorectal Dis 20:277–286. doi:10.1007/s00384-004-0639-8

    Article  PubMed  Google Scholar 

  74. Okazaki K, Morita M, Nishimori I, Sano S, Toyonaga M, Nakazawa Y et al (1993) Major histocompatibility antigen-restricted cytotoxicity in inflammatory bowel disease. Gastroenterology 104:384–391

    CAS  PubMed  Google Scholar 

  75. Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE, Perroni L et al (2006) Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 116:1713–1722. doi:10.1172/JCI25112

    Article  CAS  PubMed  Google Scholar 

  76. Ziegler SF (2006) FOXP3: of mice and men. Annu Rev Immunol 24:209–226. doi:10.1146/annurev.immunol.24.021605.090547

    Article  CAS  PubMed  Google Scholar 

  77. Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL (1993) Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol 5:1461–1471. doi:10.1093/intimm/5.11.1461

    Article  CAS  PubMed  Google Scholar 

  78. Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL (1994) Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1:553–562. doi:10.1016/1074-7613(94)90045-0

    Article  CAS  PubMed  Google Scholar 

  79. Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+) CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192:295–302. doi:10.1084/jem.192.2.295

    Article  CAS  PubMed  Google Scholar 

  80. Huibregtse IL, van Lent AU, van Deventer SJ (2007) Immunopathogenesis of IBD: insufficient suppressor function in the gut? Gut 56:584–592. doi:10.1136/gut.2006.103523

    Article  CAS  PubMed  Google Scholar 

  81. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274. doi:10.1016/0092-8674(93)80068-P

    Article  PubMed  Google Scholar 

  82. Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G et al (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98:1010–1020. doi:10.1172/JCI118861

    Article  CAS  PubMed  Google Scholar 

  83. Poutahidis T, Haigis KM, Rao VP, Nambiar PR, Taylor CL, Ge Z et al (2007) Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. Carcinogenesis 28:2614–2623. doi:10.1093/carcin/bgm180

    Article  CAS  PubMed  Google Scholar 

  84. Becker C, Fantini MC, Neurath MF (2006) TGF-beta as a T cell regulator in colitis and colon cancer. Cytokine Growth Factor Rev 17:97–106. doi:10.1016/j.cytogfr.2005.09.004

    Article  CAS  PubMed  Google Scholar 

  85. Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11:8326–8331. doi:10.1158/1078-0432.CCR-05-1244

    Article  CAS  PubMed  Google Scholar 

  86. Ishibashi Y, Tanaka S, Tajima K, Yoshida T, Kuwano H (2006) Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm. Oncol Rep 15:1315–1319

    CAS  PubMed  Google Scholar 

  87. Erdman SE, Sohn JJ, Rao VP, Nambiar PR, Ge Z, Fox JG et al (2005) CD4+ CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res 65:3998–4004. doi:10.1158/0008-5472.CAN-04-3104

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

M.F. Neurath and M.J. Waldner were supported by DFG within the Graduiertenkolleg GK 1043.

Author information

Authors and Affiliations

  1. Institute of Molecular Medicine, University of Mainz, Mainz, Germany

    Maximilian J. Waldner & Markus F. Neurath

  2. I. Department of Medicine, University of Erlangen, 91054, Erlangen, Germany

    Maximilian J. Waldner & Markus F. Neurath

Authors
  1. Maximilian J. Waldner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus F. Neurath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Markus F. Neurath.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldner, M.J., Neurath, M.F. Colitis-associated cancer: the role of T cells in tumor development. Semin Immunopathol 31, 249–256 (2009). https://doi.org/10.1007/s00281-009-0161-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-009-0161-8

Keywords

Search

Navigation