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Expression of costimulatory molecule CD80 in colonic dysplasia in ulcerative colitis: an immunosurveillance mechanism against colorectal cancer?

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Abstract

Background and aims

Ulcerative colitis is an established risk factor for colorectal cancer but dysplasia reports are much more frequent than invasive neoplasm diagnosis. The effective activation of T lymphocytes that provide antitumor surveillance requires the presence of costimulation molecules such as CD80 and CD86 on the surface of antigen-presenting cells. The aim of our study was to verify the presence of an in vivo immunosurveillance mechanism in the early stages of colon tumorigenesis.

Patients and methods

Expression of CD80, CD86, and IFNγ in the colonic mucosa of 21 consecutive ulcerative colitis (UC) patients was quantified using reverse transcription polymerase chain reaction. After a 7-year follow-up period, we reviewed the histology of all surveillance colonoscopy specimens for colonic dysplasia. Correlation, frequency, and survival analyses were performed.

Results

CD80 was detectable in seven patients while expression of CD86 and IFNγ was evident in all patients. Histology confirmed the presence of dysplasia in eight patients. Patients who had dysplasia showed higher CD80 levels compared to those without dysplasia (p=0.02). Survival analysis demonstrated that cumulative dysplasia rates of CD80-positive patients were significantly higher than those of CD80-negative patients (p=0.04).

Conclusion

Even if partially limited by a relatively small sample size, our study seems to show an association between CD80 expression and colonic dysplasia in UC patients that may suggest a role for CD80 in the immunosurveillance against colorectal cancer in this early stage of tumorigenesis. On the contrary, CD86 seems to be involved in the inflammatory pathogenesis of UC.

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References

  1. Langholz E, Munkholm P, Davidsen M, Binder V (1992) Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 103:1444–1451

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Munkholm P (2003) The incidence and prevalence of colorectal cancer in inflammatory bowel disease. Aliment Pharmacol Ther 18(Suppl 2):1–5

    Article  PubMed  Google Scholar 

  4. Itzkowitz S (2003) Colon carcinogenesis in inflammatory bowel disease. J Clin Gastroenterol 36(Suppl 1):S70–S74

    Article  PubMed  CAS  Google Scholar 

  5. Lynch DA, Lobo AJ, Sobala GM, Dixon MF, Axon AT (1993) Failure of colonoscopic surveillance in ulcerative colitis. Gut 34:1075–1080

    PubMed  CAS  Google Scholar 

  6. Lim CH, Dixon MF, Vail A, Forman D, Lynch DAF, Axon ATR (2003) Ten year follow up of ulcerative colitis patients with and without low grade dysplasia. Gut 52:1127–1132

    Article  PubMed  CAS  Google Scholar 

  7. Ugurel S, Uhlig D, Pfohler C, Tilgen W, Schadendorf D, Reinhold U (2004) Down-regulation of HLA class II and co-stimulatory CD86/B7-2 on circulating monocytes from melanoma patients. Cancer Immunol Immunother 53(6):551–559

    Article  PubMed  CAS  Google Scholar 

  8. Chouaib S, Asselin-Paturel C, Mami Chaib F, Caignard A, Blay JY (1997) The host tumour immune conflict: from immunosuppression to resistance and destruction. Immunol Today 18:493–497

    Article  PubMed  CAS  Google Scholar 

  9. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H (1998) The central role of CD4+ T cells in the antitumor immune response. J Exp Med 188(12):2357–2368

    Article  PubMed  CAS  Google Scholar 

  10. Toes REM, Ossendorp F, Offringa R, Melief CJM (1999) CD4 T cells and their role in anti-tumour immune responses. J Exp Med 189(5):753–756

    Article  PubMed  CAS  Google Scholar 

  11. Townsend SE, Allison JP (1993) Tumour rejection after direct co-stimulation of CD8+ T cells by B7 transfected melanoma cells. Science 259:368–370

    PubMed  CAS  Google Scholar 

  12. Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter JA, McGowan P, Linsey PS (1992) Costimulation of anti-tumour immunity by B7 counter receptor for T lymphocyte molecules CD28 and CTLA-4. Cell 71:1093–1102

    Article  PubMed  CAS  Google Scholar 

  13. Janeway CJ, Bottomly K (1994) Signals and signs for lymphocyte responses. Cell 76:275–285

    Article  PubMed  CAS  Google Scholar 

  14. Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349–1356

    PubMed  CAS  Google Scholar 

  15. Grewal IS, Flavell RA (1996) A central role of CD40 ligand in the regulation of CD4+ T-cell responses. Immunol Today 17:410–414

    Article  PubMed  CAS  Google Scholar 

  16. June CH, Bluestone JA, Nadler LM, Thompson CB (1994) The B7 and CD28 receptor families. Immunol Today 15:321–331

    Article  PubMed  CAS  Google Scholar 

  17. Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP (1992) CD28-mediated signalling co-stimulates T cells and prevents induction of anergy in T cell clones. Nature 356:607–609

    Article  PubMed  CAS  Google Scholar 

  18. Chaux P, Moutete M, Faivre J, Martin F, Martin M (1996) Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T- cell activation. Lab Invest 75(5):975–983

    Google Scholar 

  19. Li J, Yang Y, Inoue H, Mori M, Akiyoshi T (1996) The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon and inteleukin-10. Cancer Immunol Immunother 43:213–219

    Article  PubMed  CAS  Google Scholar 

  20. Antonia SJ, Munoz-Antonia T, Soldevila G, Miller J, Flavell RA (1995) B7-1 expression by a non-antigen presenting cell-derived tumour. Cancer Res 55(11):2253–2256

    PubMed  CAS  Google Scholar 

  21. Seo M, Okada M, Yao T, Ueki M, Arima S, Okumura M (1992) An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 87(8):971–976

    PubMed  CAS  Google Scholar 

  22. Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K (1995) Evaluation of disease activity in patients with moderately active ulcerative colitis: comparison between a new activity index and Truelove and Witts classification. Am J Gastroenterol 90(10):1759–1763

    PubMed  CAS  Google Scholar 

  23. Florén C-H, Benoni C, Willén R (1987) Histologic and colonoscopic assessment of disease extension in ulcerative colitis. Scand J Gastroenterol 22:458–462

    Google Scholar 

  24. Riddel RH (1996). Premalignant and early malignant lesions in the gastrointestinal tract: definitions, terminology and problems. Am J Gastroenterol 91(5):864–870

    PubMed  Google Scholar 

  25. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47(2):251–255

    Article  PubMed  CAS  Google Scholar 

  26. Nakazawa A, Watanabe M, Kanai T, Yajima T, Yamazaki M, Ogata H, Ishii H, Azuma M, Hibi T (1999) Functional expression of co-stimulatory molecule CD86 on epithelial cells in the inflamed colonic mucosa. Gastroenterology 117(3):726–728

    Article  PubMed  Google Scholar 

  27. Shao-Ying L, Yan-Fang S, Zeng-Shan L, Jing Y, Hai-Long D, Ping Q, Xiu-Min Z, Wen-Yong W, Yu-Song L (2004) Superantigen-SEA gene modified tumour vaccine for hepatocellular carcinoma: and in vitro study. World J Gastroenterol 10(1):53–57

    PubMed  Google Scholar 

  28. Ikeguchi M, Oi K, Hirooka Y, Kaibara N (2004) CD8+ lymphocyte infiltration and apoptosis in hepatocellular carcinoma. Eur J Surg Oncol 30:53–57

    Article  PubMed  CAS  Google Scholar 

  29. Ilkovitch D, Ostrand-Rosenberg S (2004) MC class II and CD80 tumor cell-based vaccines are potent activators of type 1 CD4+ T lymphocytes provided they do not co-express invariant chain. Cancer Immunol Immunother 53(6):525–532

    Article  PubMed  CAS  Google Scholar 

  30. Ostrand-Rosenberg S, Baskar S, Patterson N, Clements V (1996) Expression of MHC class II and B7-1 and B7-2 co-stimulatory molecules accompanies tumour rejection and reduces the metastatic potential of tumour cells. Tissue Antigens 47(5):414–421

    Article  PubMed  CAS  Google Scholar 

  31. Horig H, Lee DS, Conkright W, Divito J, Hasson H, LaMare M, Rivera A, Park D, Tine J, Guito K, Tsang KW, Schlom J, Kaufman HL (2000) Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule. Cancer Immunol Immunother 49(9):504–514

    Article  PubMed  CAS  Google Scholar 

  32. von Mehren M, Arlen P, Tsang KY, Rogatko A, Meropol N, Cooper HS, Davey M, McLaughlin S, Schlom J, Weiner LM (2000) Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. Clin Cancer Res 6(6):2219–2228

    PubMed  Google Scholar 

  33. Scarpa M, Behboo R, Angriman I, Termini B, Barollo M, Ruffolo C, Polese L, D’Incà R, Sturniolo GC, D’Amico DF (2004) The role of co-stimulatory molecules CD80 and CD86 and IFNγ in the pathogenesis of ulcerative colitis. Dig Dis Sci 49(11–12):1738–1744

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We are very grateful to Joanne Stempak, Research Coordinator at the Mount Sinai Hospital of Toronto, Canada, for her competent and careful revision of the English language.

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Authors and Affiliations

  1. Dipartimento di Scienze Chirurgiche e Gastroenterologiche, sez. di Clinica Chirurgica I, University of Padova, via Giustiniani 2, Padova, 35128, Italy

    Marco Scarpa, Imerio Angriman, Barbara Termini, Michela Barollo, Cesare Ruffolo, Lino Polese & Davide Francesco D’Amico

  2. Dipartimento di Scienze Chirurgiche e Gastroenterologiche, sez. di Endocrinochirurgia, University of Padova, Padova, Italy

    Roubik Behboo

  3. Dipartimento di Scienze Chirurgiche e Gastroenterologiche, sez. di Gastroenterologia, University of Padova, Padova, Italy

    Renata D’Incà & Giacomo Carlo Sturniolo

  4. Istituto di Anatomia Patologica, University of Padova, Padova, Italy

    Attilio Cecchetto

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  1. Marco Scarpa
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Correspondence to Imerio Angriman.

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Scarpa, M., Behboo, R., Angriman, I. et al. Expression of costimulatory molecule CD80 in colonic dysplasia in ulcerative colitis: an immunosurveillance mechanism against colorectal cancer?. Int J Colorectal Dis 21, 776–783 (2006). https://doi.org/10.1007/s00384-006-0095-8

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