Asian Pacific Journal of Cancer Prevention

  • 제16권13호
  • /
  • Pages.5359-5364
  • /
  • 2015
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Expression of Granulysin and FOXP3 in Cutaneous T Cell Lymphoma and Sézary Syndrome

  • 발행 : 2015.08.03
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form ;$s\acute{e}ezary$ syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.

키워드

참고문헌

  1. Alcantara-Hernandez M, Torres-Zarate C, Perez-Montesinos G, et al (2014). Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications. Int J Cancer, 134, 2136-45. https://doi.org/10.1002/ijc.28546
  2. Banham AH, Brown PJ, Lyne L, et al (2008). Is FOXP3 expressed in cutaneous T-cell lymphomas? Eur J Haematol, 80, 90-1.
  3. Berger CL, Tigelaar R, Cohen J, et al (2005). Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood, 105, 1640-7. https://doi.org/10.1182/blood-2004-06-2181
  4. Capriotti E, Vonderheid EC, Thoburn CJ, et al (2008). Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leuk Lymphoma, 49, 1190-201. https://doi.org/10.1080/10428190802064917
  5. Clark RA (2009). Regulation gone wrong: a subset of Sezary patients have malignant regulatory T cells. J Invest Dermatol, 129, 2747-50. https://doi.org/10.1038/jid.2009.290
  6. Du Y, Chen X, Huang ZM, et al (2012). Increased frequency of Foxp3+ regulatory T cells in mice with hepatocellular carcinoma. Asian Pac J Cancer Prev, 13, 3815-9. https://doi.org/10.7314/APJCP.2012.13.8.3815
  7. Edelson RL (2001). Cutaneous T cell lymphoma: the helping hand of dendritic cells. Ann N Y Acad Sci, 941, 1-11.
  8. Escher N, Spies-Weisshart B, Kaatz M, et al (2006). Identification of HNP3 as a tumour marker in CD4+ and CD4-lymphocytes of patients with cutaneous T-cell lymphoma. Eur J Cancer, 42, 249-55. https://doi.org/10.1016/j.ejca.2005.07.033
  9. Fried I, Cerroni L (2012). FOXP3 in sequential biopsies of progressive mycosis fungoides. Am J Dermatopathol, 34, 263-5. https://doi.org/10.1097/DAD.0b013e31823062db
  10. Fujimura T, Okuyama R, Ito Y, et al (2008). Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides. Br J Dermatol, 158, 1256-63. https://doi.org/10.1111/j.1365-2133.2008.08504.x
  11. Gjerdrum LM, Woetmann A, Odum N, et al (2007). FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival. Leukemia, 21, 2512-8. https://doi.org/10.1038/sj.leu.2404913
  12. Hallermann C, Niermann C, Schulze HJ (2007). Regulatory T-cell phenotype in association with large cell transformation of mycosis fungoides. Eur J Haematol, 78, 260-3. https://doi.org/10.1111/j.1600-0609.2006.00809.x
  13. Hanafusa T, Matsui S, Murota H, et al (2013). Increased frequency of skin-infiltrating FoxP3+ regulatory T cells as a diagnostic indicator of severe atopic dermatitis from cutaneous T cell lymphoma. Clin Exp Immunol, 172, 507-12. https://doi.org/10.1111/cei.12073
  14. Heid JB, Schmidt A, Oberle N, et al (2009). FOXP3+CD25-tumor cells with regulatory function in Sezary syndrome. J Invest Dermatol, 129, 2875-85. https://doi.org/10.1038/jid.2009.175
  15. Jawed SI, Myskowski PL, Horwitz S, et al (2014). Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers. J Am Acad Dermatol, 70, 1-16.
  16. Johnson VE, Vonderheid EC, Hess AD, et al (2014). Genetic markers associated with progression in early mycosis fungoides. J Eur Acad Dermatol Venereol, 28, 1431-5. https://doi.org/10.1111/jdv.12299
  17. Kasprzycka M, Zhang Q, Witkiewicz A, et al (2008). Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes. J Immunol, 181, 2506-12. https://doi.org/10.4049/jimmunol.181.4.2506
  18. Kelley TW, Parker CJ (2010). CD4 (+)CD25 (+)Foxp3 (+) regulatory T cells and hematologic malignancies. Front Biosci (Schol Ed), 2, 980-92.
  19. Kishi A, Takamori Y, Ogawa K, et al (2002). Differential expression of granulysin and perforin by NK cells in cancer patients and correlation of impaired granulysin expression with progression of cancer. Cancer Immunol Immunother, 50, 604-14. https://doi.org/10.1007/s002620100228
  20. Klemke CD, Fritzsching B, Franz B, et al (2006). Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sezary syndrome from other cutaneous T-cell lymphomas. Leukemia, 20, 1123-9. https://doi.org/10.1038/sj.leu.2404182
  21. Marzano AV, Vezzoli P, Fanoni D, et al (2009). Primary cutaneous T-cell lymphoma expressing FOXP3: a case report supporting the existence of malignancies of regulatory T cells. J Am Acad Dermatol, 61, 348-55. https://doi.org/10.1016/j.jaad.2008.11.894
  22. Nagasawa M, Kawamoto H, Tsuji Y, et al (2005). Transient increase of serum granulysin in a stage IVs neuroblastoma patient during spontaneous regression: case report. Int J Hematol, 82, 456-7. https://doi.org/10.1532/IJH97.05091
  23. Okada S, Morishita T (2012). The Role of Granulysin in Cancer Immunology. ISRN Immunology, 2012, 5.
  24. Quaglino P, Pimpinelli N, Berti E, et al (2012). Mycosis fungoides: disease evolution of the "lion queen" revisited. G Ital Dermatol Venereol, 147, 523-31.
  25. Saigusa S, Ichikura T, Tsujimoto H, et al (2007). Serum granulysin level as a novel prognostic marker in patients with gastric carcinoma. J Gastroenterol Hepatol, 22, 1322-7. https://doi.org/10.1111/j.1440-1746.2006.04796.x
  26. Sekiguchi N, Asano N, Ito T, et al (2012). Elevated serum granulysin and its clinical relevance in mature NK-cell neoplasms. Int J Hematol, 96, 461-8. https://doi.org/10.1007/s12185-012-1159-x
  27. Solomon GJ, Magro CM (2008). Foxp3 expression in cutaneous T-cell lymphocytic infiltrates. J Cutan Pathol, 35, 1032-9. https://doi.org/10.1111/j.1600-0560.2007.00969.x
  28. Tiemessen MM, Mitchell TJ, Hendry L, et al (2006). Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma. J Invest Dermatol, 126, 2217-23. https://doi.org/10.1038/sj.jid.5700371
  29. Wada DA, Pittelkow MR, Comfere NI, et al (2013). CD4(+) CD25(+)FOXP3(+) malignant T cells in Sezary syndrome are not necessarily functional regulatory T cells. J Am Acad Dermatol, 69, 485-9.
  30. Wada DA, Wilcox RA, Weenig RH, et al (2010). Paucity of intraepidermal FoxP3-positive T cells in cutaneous T-cell lymphoma in contrast with spongiotic and lichenoid dermatitis. J Cutan Pathol, 37, 535-41. https://doi.org/10.1111/j.1600-0560.2009.01381.x
  31. Wang G (2014). Human antimicrobial peptides and proteins. Pharmaceuticals (Basel), 7, 545-94. https://doi.org/10.3390/ph7050545
  32. Wilcox RA (2014). Cutaneous T-cell lymphoma: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol, 89, 837-51. https://doi.org/10.1002/ajh.23756
  33. Willemze R, Jaffe ES, Burg G, et al (2005). WHO-EORTC classification for cutaneous lymphomas. Blood, 105, 3768-85. https://doi.org/10.1182/blood-2004-09-3502
  34. Willerslev-Olsen A, Krejsgaard T, Lindahl LM, et al (2013). Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma. Toxins (Basel), 5, 1402-21. https://doi.org/10.3390/toxins5081402
  35. Zhan HL, Gao X, Zhou XF, et al (2012). Presence of tumourinfiltrating FOXP3+ lymphocytes correlates with immature tumour angiogenesis in renal cell carcinomas. Asian Pac J Cancer Prev, 13, 867-72. https://doi.org/10.7314/APJCP.2012.13.3.867
  36. Zhang GQ, Han F, Fang XZ, et al (2012). CD4+, IL17 and Foxp3 expression in different pTNM stages of operable non-small cell lung cancer and effects on disease prognosis. Asian Pac J Cancer Prev, 13, 3955-60. https://doi.org/10.7314/APJCP.2012.13.8.3955
  37. Zhou QY, Wang YL, Li X, et al (2014). Metabolomics investigation of cutaneous T cell lymphoma based on UHPLC-QTOF/MS. Asian Pac J Cancer Prev, 15, 5417-21. https://doi.org/10.7314/APJCP.2014.15.13.5417
  38. Zou W (2006). Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol, 6, 295-307. https://doi.org/10.1038/nri1806

피인용 문헌

  1. Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and Sézary syndrome vol.67, pp.3, 2018, https://doi.org/10.1007/s00262-017-2090-z
  2. Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type pp.1432-2307, 2018, https://doi.org/10.1007/s00428-018-2434-x