Pathology & Oncology Research

, Volume 18, Issue 4, pp 749–759 | Cite as

Tissue-Specific Homing of Immune Cells in Malignant Skin Tumors

  • Hajnalka Jókai
  • Márta Marschalkó
  • Judit Csomor
  • József Szakonyi
  • Orsolya Kontár
  • Gábor Barna
  • Sarolta Kárpáti
  • Péter Holló
Review

Abstract

Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral non-lymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by non-lymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sézary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.

Keywords

Lymphocyte homing receptors Cutaneous lymphocyte associated antigen Malignant melanoma Basal cell carcinoma Squamous cell carcinoma Cutaneous T-cell lymphoma 

Abbreviations

Tem

effector memory T lymphocytes

Tcm

central memory T lymphocytes

CLA

cutaneous lymphocyte associated antigen

PSGL-1

P-selectin glycoprotein ligand 1

DC

dendritic cells

TILs

tumor infiltrating lymphocytes

Treg cells

regulatory T cells

LFA-1

leukocyte function associated antigen 1

VLA-4

very late antigen 4

ICAM

intercellular adhesion molecule

VCAM

vascular cell adhesion molecule

VEGF

vascular endothelial growth factor

TGF

fibroblast growth factor

SCC

squamous cell carcinoma

iNOS

inducible NO synthetase

BCC

basal cell carcinoma

CTCL

cutaneous T cell lymphoma

SS

Sézary-syndrome

MF

mycosis fungoides

SDF-1

stromal cell-derived factor 1

References

  1. 1.
    Kunkel EJ, Butcher EC (2002) Chemokines and the tissue-specific migration of lymphocytes. Immunity 16:1–4PubMedCrossRefGoogle Scholar
  2. 2.
    Hart AL, Ng SC, Mann E, Al-Hassi HO, Bernardo D, Knight SC (2010) Homing of immune cells: role in homeostasis and intestinal inflammation. Inflamm Bowel Dis 16:1969–1977PubMedCrossRefGoogle Scholar
  3. 3.
    Lalor PF, Curbishley SM, Adams DH (2010) Identifying homing interactions in T-cell traffic in human disease. Methods Mol Biol 616:231–252PubMedCrossRefGoogle Scholar
  4. 4.
    Villablanca EJ, Russo V, Mora JR (2008) Dendritic cell migration and lymphocyte homing imprinting. Histol Histopathol 23:897–910PubMedGoogle Scholar
  5. 5.
    Woodland DL, Kohlmeier JE (2009) Migration, maintenance and recall of memory T cells in peripheral tissues. Nat Rev Immunol 9:153–161PubMedCrossRefGoogle Scholar
  6. 6.
    Sigmundsdottir H, Butcher EC (2008) Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking. Nat Immunol 9:981–987PubMedCrossRefGoogle Scholar
  7. 7.
    Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ (2009) Skin immune sentinels in health and disease. Nat Rev Immunol 9:679–691PubMedGoogle Scholar
  8. 8.
    Clark RA (2010) Skin-resident T cells: the ups and downs of on site immunity. J Invest Dermatol 130(2):362–370PubMedCrossRefGoogle Scholar
  9. 9.
    Sigmundsdottir H (2010) Improving topical treatments for skin diseases. Trends Pharmacol Sci 31:239–245PubMedCrossRefGoogle Scholar
  10. 10.
    Fuhlbrigge RC, King SL, Sackstein R, Kupper TS (2006) CD43 is a ligand for E-selectin on CLA + human T cells. Blood 107:1421–1426PubMedCrossRefGoogle Scholar
  11. 11.
    Magro CM, Dyrsen ME (2008) Cutaneous lymphocyte antigen expression in benign and neoplastic cutaneous B- and T-cell lymphoid infiltrates. J Cutan Pathol 35:1040–1049PubMedCrossRefGoogle Scholar
  12. 12.
    Ni Z, Walcheck B (2009) Cutaneous lymphocyte-associated antigen (CLA) T cells up-regulate P-selectin ligand expression upon their activation. Clin Immunol 133:257–264PubMedCrossRefGoogle Scholar
  13. 13.
    Yamanaka K, Dimitroff CJ, Fuhlbrigge RC, Kakeda M, Kurokawa I, Mizutani H, Kupper TS (2008) Vitamins A and D are potent inhibitors of cutaneous lymphocyte-associated antigen expression. J Allergy Clin Immunol 121:148–157.e3Google Scholar
  14. 14.
    Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496PubMedCrossRefGoogle Scholar
  15. 15.
    Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F (2009) Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10:857–863PubMedCrossRefGoogle Scholar
  16. 16.
    Zlotnik A, Yoshie O (2000) Chemokines: a new classification system and their role in immunity. Immunitiy 12:121–127CrossRefGoogle Scholar
  17. 17.
    Sabat R, Philipp S, Höflich C, Kreutzer S, Wallace E, Asadullah K, Volk HD, Sterry W, Wolk K (2007) Immunopathogenesis of psoriasis. Exp Dermatol 16:779–798PubMedCrossRefGoogle Scholar
  18. 18.
    Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K, Dowgiert RK, Kupper TS (2006) The vast majority of CLA + T cells are resident in normal skin. J Immunol 176:4431–4439PubMedGoogle Scholar
  19. 19.
    Santamaria Babi LF, Moser R, Perez Soler MT, Picker LJ, Blaser K, Hauser C (1995) Migration of skin-homing T cells across cytokine-activated human endothelial cell layers involves interaction of the cutaneous lymphocyte-associated antigen (CLA), the very late antigen-4 (VLA-4), and the lymphocyte function-associated antigen-1 (LFA-1). J Immunol 154:1543–1550PubMedGoogle Scholar
  20. 20.
    Pals ST, de Gorter DJ, Spaargaren M (2007) Lymphoma dissemination: the other face of lymphocyte homing. Blood 110:3102–3111PubMedCrossRefGoogle Scholar
  21. 21.
    Gelb AB, Smoller BR, Warnke RA, Picker LJ (1993) Lymphocytes infiltrating primary cutaneous neoplasms selectively express the cutaneous lymphocyte-associated antigen (CLA). Am J Pathol 142:1556–1564PubMedGoogle Scholar
  22. 22.
    Clark WH Jr, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727PubMedGoogle Scholar
  23. 23.
    Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310PubMedCrossRefGoogle Scholar
  24. 24.
    Mullins IM, Slingluff CL, Lee JK, Garbee CF, Shu J, Anderson SG, Mayer ME, Knaus WA, Mullins DW (2004) CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with survival in melanoma patients with stage III disease. Cancer Res 64:7697–7701PubMedCrossRefGoogle Scholar
  25. 25.
    Day CL Jr, Sober AJ, Kopf AW, Lew RA, Mihm MC Jr, Hennessey P, Golomb FM, Harris MN, Gumport SL, Raker JW, Malt RA, Cosimi AB, Wood WC, Roses DF, Gorstein F, Postel A, Grier WR, Mintzis MN, Fitzpatrick TB (1981) A prognostic model for clinical stage I melanoma of the upper extremity. The importance of anatomic subsites in predicting recurrent disease. Ann Surg 193:436–440PubMedCrossRefGoogle Scholar
  26. 26.
    Tuthill RJ, Unger JM, Liu PY, Flaherty LE, Sondak VK (2002) Risk assessment in localized primary cutaneous melanoma: a Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am J Clin Pathol 118:504–511PubMedCrossRefGoogle Scholar
  27. 27.
    Oble DA, Loewe R, Yu P, Mihm MC Jr (2009) Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun 9:3PubMedGoogle Scholar
  28. 28.
    Taylor RC, Patel A, Panageas KS, Busam KJ, Brady MS (2007) Tumor-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. J Clin Oncol 25:869–875PubMedCrossRefGoogle Scholar
  29. 29.
    Prieto PA, Durflinger KH, Wunderlich JR, Rosenberg SA, Dudley ME (2010) Enrichment of CD8+ cells from melanoma tumor-infiltrating lymphocyte cultures reveals tumor reactivity for use in adoptive cell therapy. J Immunother 33:547–556PubMedCrossRefGoogle Scholar
  30. 30.
    Viguier M, Lemaître F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L (2004) Foxp3 expressing CD4 + CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173:1444–1453PubMedGoogle Scholar
  31. 31.
    Weishaupt C, Munoz KN, Buzney E, Kupper TS, Fuhlbrigge RC (2007) T-cell distribution and adhesion receptor expression in metastatic melanoma. Clin Cancer Res 13:2549–2556PubMedCrossRefGoogle Scholar
  32. 32.
    Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8:299–308PubMedCrossRefGoogle Scholar
  33. 33.
    Labarriere N, Dreno B, Jotereau F (2008) Lymphocyte biomarkers of clinical responses to adoptive immunotherapy of malignant melanoma. Curr Cancer Ther Rev 4:125–129CrossRefGoogle Scholar
  34. 34.
    Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP (2006) Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 6:383–393PubMedCrossRefGoogle Scholar
  35. 35.
    Adams DH, Yannelli JR, Newman W, Lawley T, Ades E, Rosenberg SA, Shaw S (1997) Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis. Br J Cancer 75:1421–1431PubMedCrossRefGoogle Scholar
  36. 36.
    Rohde D, Schlüter-Wigger W, Mielke V, von den Driesch P, von Gaudecker B, Sterry W (1992) Infiltration of both T cells and neutrophils in the skin is accompanied by the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1): an immunohistochemical and ultrastructural study. J Invest Dermatol 98:794–799PubMedCrossRefGoogle Scholar
  37. 37.
    Schadendorf D, Heidel J, Gawlik C, Suter L, Czarnetzki BM (1995) Association with clinical outcome of expression of VLA-4 in primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels. J Natl Cancer Inst 87:366–371PubMedCrossRefGoogle Scholar
  38. 38.
    Nooijen PT, Westphal JR, Eggermont AM, Schalkwijk C, Max R, de Waal RM, Ruiter DJ (1998) Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis. Am J Pathol 152:679–682PubMedGoogle Scholar
  39. 39.
    Quezada SA, Peggs KS, Simpson TR, Shen Y, Littman DR, Allison JP (2008) Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. J Exp Med 205:2125–2138PubMedCrossRefGoogle Scholar
  40. 40.
    Walshe TE, Dole VS, Maharaj AS, Patten IS, Wagner DD, D'Amore PA (2009) Inhibition of VEGF or TGF-{beta} signaling activates endothelium and increases leukocyte rolling. Arterioscler Thromb Vasc Biol 29:1185–1192PubMedCrossRefGoogle Scholar
  41. 41.
    Walshe TE (2010) TGF-beta and microvessel homeostasis. Microvasc Res 80:166–173PubMedCrossRefGoogle Scholar
  42. 42.
    Kiss J, Tímár J, Somlai B, Gilde K, Fejôs Z, Gaudi I, Ladányi A (2007) Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma. Pathol Oncol Res 13:21–31PubMedCrossRefGoogle Scholar
  43. 43.
    Barton GM (2008) A calculated response: control of inflammation by the innate immune system. J Clin Invest 118:413–420PubMedCrossRefGoogle Scholar
  44. 44.
    Krieg C, Boyman O (2009) The role of chemokines in cancer immune surveillance by the adaptive immune system. Semin Cancer Biol 19:76–83PubMedCrossRefGoogle Scholar
  45. 45.
    Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF (2009) Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res 69:3077–3085PubMedCrossRefGoogle Scholar
  46. 46.
    Navarini-Meury AA, Conrad C (2009) Melanoma and innate immunity–aActive inflammation or just erroneous attraction? Melanoma as the source of leukocyte-attracting chemokines. Semin Cancer Biol 19:84–91PubMedCrossRefGoogle Scholar
  47. 47.
    Richmond A, Yang J, Su Y (2009) The good and the bad of chemokines/chemokine receptors in melanoma. Pigment Cell Melanoma Res 22:175–186PubMedCrossRefGoogle Scholar
  48. 48.
    Somasundaram R, Herlyn D (2009) Chemokines and the microenvironment in neuroectodermal tumor-host interaction. Semin Cancer Biol 19:92–96PubMedCrossRefGoogle Scholar
  49. 49.
    Strieter RM, Belperio JA, Phillips RJ, Keane MP (2004) CXC chemokines in angiogenesis of cancer. Semin Cancer Biol 14:195–200PubMedCrossRefGoogle Scholar
  50. 50.
    Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP (2005) CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 16:593–609PubMedCrossRefGoogle Scholar
  51. 51.
    Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K (1998) Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187:2009–2021PubMedCrossRefGoogle Scholar
  52. 52.
    Kunz M, Toksoy A, Goebeler M, Engelhardt E, Brocker E, Gillitzer R (1999) Strong expression of the lymphoattractant C-X-C chemokine Mig is associated with heavy infiltration of T cells in human malignant melanoma. J Pathol 189:552–558PubMedCrossRefGoogle Scholar
  53. 53.
    Graves DT, Barnhill R, Galanopoulos T, Antoniades HN (1992) Expression of monocyte chemotactic protein-1 in human melanoma in vivo. Am J Pathol 140:9–14PubMedGoogle Scholar
  54. 54.
    Mellado M, de Ana AM, Moreno MC, Martinez C, Rodriguez-Frade JM (2001) A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Curr Biol 11:691–696PubMedCrossRefGoogle Scholar
  55. 55.
    Fushimi T, Kojima A, Moore MA, Crystal RG (2000) Macrophage inflammatory protein 3alpha transgene attracts dendritic cells to established murine tumors and suppresses tumor growth. J Clin Invest 105:1383–1393PubMedCrossRefGoogle Scholar
  56. 56.
    Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62:6997–7000PubMedGoogle Scholar
  57. 57.
    Robertson GP (2005) Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev 24:273–285PubMedCrossRefGoogle Scholar
  58. 58.
    Hardy KM, Kirschmann DA, Seftor EA, Margaryan NV, Postovit LM, Strizzi L, Hendrix MJ (2010) Regulation of the embryonic morphogen Nodal by Notch4 facilitates manifestation of the aggressive melanoma phenotype. Cancer Res 70:10340–10350PubMedCrossRefGoogle Scholar
  59. 59.
    Yang CH, Fan M, Slominski AT, Yue J, Pfeffer LM (2010) The role of constitutively activated STAT3 in B16 melanoma cells. Int J Interferon Cytokine Mediator Res 2010:1–7Google Scholar
  60. 60.
    Clark RA, Chong BF, Mirchandani N, Yamanaka K, Murphy GF, Dowgiert RK, Kupper TS (2006) A novel method for the isolation of skin resident T cells from normal and diseased human skin. J Invest Dermatol 126:1059–1070PubMedCrossRefGoogle Scholar
  61. 61.
    Clark RA, Huang SJ, Murphy GF, Mollet IG, Hijnen D, Muthukuru M, Schanbacher CF, Edwards V, Miller DM, Kim JE, Lambert J, Kupper TS (2008) Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells. J Exp Med 205:2221–2234PubMedCrossRefGoogle Scholar
  62. 62.
    Hald J, Rasmussen N, Claesson MH (1995) Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck. Cancer Immunol Immunother 41:243–250PubMedCrossRefGoogle Scholar
  63. 63.
    Wei S, Kryczek I, Zou W (2006) Regulatory T-cell compartmentalization and trafficking. Blood 108:426–431PubMedCrossRefGoogle Scholar
  64. 64.
    Dummer R, Urosevic M, Kempf W, Hoek K, Hafner J, Burg G (2003) Imiquimod in basal cell carcinoma: how does it work? Br J Dermatol 149(Suppl 66):57–58PubMedCrossRefGoogle Scholar
  65. 65.
    Urosevic M, Maier T, Benninghoff B, Slade H, Burg G, Dummer R (2003) Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo. Arch Dermatol 139:1325–1332PubMedCrossRefGoogle Scholar
  66. 66.
    Verhaegh M, Beljaards R, Veraart J, Hoekzema R, Neumann M (1998) Adhesion molecule expression in basal cell carcinoma. Eur J Dermatol 8:252–255PubMedGoogle Scholar
  67. 67.
    Kooy AJ, Prens EP, Van Heukelum A, Vuzevski VD, Van Joost T, Tank B (1999) Interferon-gamma-induced ICAM-1 and CD40 expression, complete lack of HLA-DR and CD80 (B7.1), and inconsistent HLA-ABC expression in basal cell carcinoma: a possible role for interleukin-10? J Pathol 187:351–357PubMedCrossRefGoogle Scholar
  68. 68.
    Kooy AJ, Tank B, Vuzevski VD, van Joost T, Prens EP (1998) Expression of interferongamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFNgamma R and shedding of ICAM-1 as a means to escape immune surveillance. J Pathol 184:169–176PubMedCrossRefGoogle Scholar
  69. 69.
    Kovach BT, Stasko T (2005) Use of topical immunomodulators in organ transplant recipients. Dermatol Ther 18:19–27PubMedCrossRefGoogle Scholar
  70. 70.
    Barnetson RS, Satchell A, Zhuang L, Slade HB, Halliday GM (2004) Imiquimod induced regression of clinically diagnosed superficial basal cell carcinoma is associated with early infiltration by CD4 T cells and dendritic cells. Clin Exp Dermatol 29:639–643PubMedCrossRefGoogle Scholar
  71. 71.
    De Giorgi V, Salvini C, Chiarugi A, Paglierani M, Maio V, Nicoletti P, Santucci M, Carli P, Massi D (2009) In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma. Int J Dermatol 48:312–321PubMedCrossRefGoogle Scholar
  72. 72.
    Salasche S (2002) Imiquimod 5 % cream: a new treatment option for basal cell carcinoma. Int J Dermatol 41(Suppl 1):16–20PubMedCrossRefGoogle Scholar
  73. 73.
    Kaporis HG, Guttman-Yassky E, Lowes MA, Haider AS, Fuentes-Duculan J, Darabi K, Whynot-Ertelt J, Khatcherian A, Cardinale I, Novitskaya I, Krueger JG, Carucci JA (2007) Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment. J Invest Dermatol 127:2391–2398PubMedCrossRefGoogle Scholar
  74. 74.
    Kim EJ, Hess S, Richardson SK, Newton S, Showe LC, Benoit BM, Ubriani R, Vittorio CC, Junkins-Hopkins JM, Wysocka M, Rook AH (2005) Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest 115:798–812PubMedGoogle Scholar
  75. 75.
    Berger CL, Tigelaar R, Cohen J, Mariwalla K, Trinh J, Wang N, Edelson RL (2005) Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood 105:1640–1647PubMedCrossRefGoogle Scholar
  76. 76.
    Clark RA (2009) Regulation gone wrong: a subset of Sézary patients have malignant regulatory T cells. J Invest Dermatol 129:2747–2750PubMedCrossRefGoogle Scholar
  77. 77.
    Chong BF, Wilson AJ, Gibson HM, Hafner MS, Luo Y, Hedgcock CJ, Wong HK (2008) Immune function abnormalities in peripheral blood mononuclear cell cytokine expression differentiates stages of cutaneous T-cell lymphoma/mycosis fungoides. Clin Cancer Res 14:646–653PubMedCrossRefGoogle Scholar
  78. 78.
    Beyer M, Möbs M, Humme D, Sterry W (2011) Pathogenesis of mycosis fungoides. J Dtsch Dermatol Ges 9:594–598PubMedGoogle Scholar
  79. 79.
    Heid JB, Schmidt A, Oberle N, Goerdt S, Krammer PH, Suri-Payer E, Klemke CD (2009) FOXP3 + CD25- tumor cells with regulatory function in Sézary syndrome. J Invest Dermatol 129:2875–2885PubMedCrossRefGoogle Scholar
  80. 80.
    Capriotti E, Vonderheid EC, Thoburn CJ, Wasik MA, Bahler DW, Hess AD (2008) Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leuk Lymphoma 49:1190–1201PubMedCrossRefGoogle Scholar
  81. 81.
    Krejsgaard T, Gjerdrum LM, Ralfkiaer E, Lauenborg B, Eriksen KW, Mathiesen AM, Bovin LF, Gniadecki R, Geisler C, Ryder LP, Zhang Q, Wasik MA, Odum N, Woetmann (2008) A Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome. Leukemia 22:2230–2239PubMedCrossRefGoogle Scholar
  82. 82.
    Bouaziz JD, Remtoula N, Bensussan A, Marie-Cardine A, Bagot M (2010) Absolute CD3+ CD158k + lymphocyte count is reliable and more sensitive than cytomorphology to evaluate blood tumor burden in Sézary syndrome. Br J Dermatol 162:123–128PubMedCrossRefGoogle Scholar
  83. 83.
    Campbell JJ, Clark RA, Watanabe R, Kupper TS (2010) Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 116:767–771PubMedCrossRefGoogle Scholar
  84. 84.
    Notohamiprodjo M, Segerer S, Huss R, Hildebrandt B, Soler D, Djafarzadeh R, Buck W, Nelson PJ, von Luettichau I (2005) CCR10 is expressed in cutaneous T-cell lymphoma. Int J Cancer 115:641–647PubMedCrossRefGoogle Scholar
  85. 85.
    Hwang ST, Janik JE, Jaffe ES, Wilson WH (2008) Mycosis fungoides and Sézary syndrome. Lancet 371:945–957PubMedCrossRefGoogle Scholar
  86. 86.
    Narducci MG, Scala E, Bresin A, Caprini E, Picchio MC, Remotti D, Ragone G, Nasorri F, Frontani M, Arcelli D, Volinia S, Lombardo GA, Baliva G, Napolitano M, Russo G (2006) Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV. Blood 107:1108–1115PubMedCrossRefGoogle Scholar
  87. 87.
    Wu XS, Lonsdorf AS, Hwang ST (2009) Cutaneous T-cell lymphoma: roles for chemokines and chemokine receptors. J Invest Dermatol 129:1115–1119PubMedCrossRefGoogle Scholar
  88. 88.
    Capriotti E, Vonderheid EC, Thoburn CJ, Bright EC, Hess AD (2007) Chemokine receptor expression by leukemic T cells of cutaneous T-cell lymphoma: clinical and histopathological correlations. J Invest Dermatol 127:2882–2892PubMedCrossRefGoogle Scholar
  89. 89.
    Sokolowska-Wojdylo M, Wenzel J, Gaffal E, Lenz J, Speuser P, Erdmann S, Abuzahra F, Bowman E, Roszkiewicz J, Bieber T, Tüting T (2005) Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7. Br J Dermatol 152:258–264PubMedCrossRefGoogle Scholar
  90. 90.
    Drillenburg P, Pals ST (2000) Cell adhesion receptors in lymphoma dissemination. Blood 95:1900–1910PubMedGoogle Scholar
  91. 91.
    Borowitz MJ, Weidner A, Olsen EA, Picker LJ (1993) Abnormalities of circulating T-cell subpopulations in patients with cutaneous T-cell lymphoma: cutaneous lymphocyte-associated antigen expression on T cells correlates with extent of disease. Leukemia 7:859–863PubMedGoogle Scholar
  92. 92.
    Heald PW, Yan SL, Edelson RL, Tigelaar R, Picker LJ (1993) Skin-selective lymphocyte homing mechanisms in the pathogenesis of leukemic cutaneous T-cell lymphoma. J Invest Dermatol 101:222–226PubMedCrossRefGoogle Scholar
  93. 93.
    Chong BF, Murphy JE, Kupper TS, Fuhlbrigge RC (2004) E-selectin, thymus- and activation-regulated chemokine/CCL17, and intercellular adhesion molecule-1 are constitutively coexpressed in dermal microvessels: a foundation for a cutaneous immunosurveillance system. J Immunol 172:1575–1581PubMedGoogle Scholar
  94. 94.
    Hoeller C, Richardson SK, Ng LG, Valero T, Wysocka M, Rook AH, Weninger W (2009) In vivo imaging of cutaneous T-cell lymphoma migration to the skin. Cancer Res 69:2704–2708PubMedCrossRefGoogle Scholar
  95. 95.
    Wu CS, Wang ST, Liao CY, Wu MT (2008) Differential CCR4 expression and function in cutaneous T-cell lymphoma cell lines. Kaohsiung J Med Sci 24:577–590PubMedCrossRefGoogle Scholar
  96. 96.
    Santamaria-Babí LF (2004) CLA(+) T cells in cutaneous diseases. Eur J Dermatol 14:13–18PubMedGoogle Scholar
  97. 97.
    Saeki H, Tamaki K (2006) Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J Dermatol Sci 43:75–84PubMedCrossRefGoogle Scholar
  98. 98.
    Yagi H, Seo N, Ohshima A, Itoh T, Itoh N, Horibe T, Yoshinari Y, Takigawa M, Hashizume H (2006) Chemokine receptor expression in cutaneous T cell and NK/T-cell lymphomas: immunohistochemical staining and in vitro chemotactic assay. Am J Surg Pathol 30:1111–1119PubMedGoogle Scholar
  99. 99.
    Kakinuma T, Sugaya M, Nakamura K, Kaneko F, Wakugawa M, Matsushima K, Tamaki K (2003) Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol 48:23–30PubMedCrossRefGoogle Scholar
  100. 100.
    Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS (2002) Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol 119:1405–1410PubMedCrossRefGoogle Scholar
  101. 101.
    Fierro MT, Comessatti A, Quaglino P, Ortoncelli M, Osella Abate S, Ponti R, Novelli M, Bernengo MG (2006) Expression pattern of chemokine receptors and chemokine release in inflammatory erythroderma and Sézary syndrome. Dermatology 213:284–292PubMedCrossRefGoogle Scholar
  102. 102.
    Sugaya M (2010) Chemokines and cutaneous lymphoma. J Dermatol Sci 59:81–85PubMedCrossRefGoogle Scholar
  103. 103.
    Kagami S, Sugaya M, Minatani Y, Ohmatsu H, Kakinuma T, Fujita H, Tamaki K (2006) Elevated serum CTACK/CCL27 levels in CTCL. J Invest Dermatol 126:1189–1191PubMedCrossRefGoogle Scholar
  104. 104.
    Fujita Y, Abe R, Sasaki M, Honda A, Furuichi M, Asano Y, Norisugi O, Shimizu T, Shimizu H (2006) Presence of circulating CCR10+ T cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides. Clin Cancer Res 12:2670–2675PubMedCrossRefGoogle Scholar
  105. 105.
    Lu D, Duvic M, Medeiros LJ, Luthra R, Dorfman DM, Jones D (2001) The T-cell chemokine receptor CXCR3 is expressed highly in low-grade mycosis fungoides. Am J Clin Pathol 115:413–421PubMedCrossRefGoogle Scholar
  106. 106.
    Kallinich T, Muche JM, Qin S, Sterry W, Audring H, Kroczek RA (2003) Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. J Invest Dermatol 121:1045–1052PubMedCrossRefGoogle Scholar
  107. 107.
    Yamaguchi T, Ohshima K, Tsuchiya T, Suehuji H, Karube K, Nakayama J, Suzumiya J, Yoshino T, Kikuchi M (2003) The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2- associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma. Eur J Dermatol 13:553–559PubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2012

Authors and Affiliations

  • Hajnalka Jókai
    • 1
  • Márta Marschalkó
    • 1
  • Judit Csomor
    • 2
  • József Szakonyi
    • 1
  • Orsolya Kontár
    • 1
  • Gábor Barna
    • 2
  • Sarolta Kárpáti
    • 1
    • 3
  • Péter Holló
    • 1
  1. 1.Department of Dermatovenerology and DermatooncologySemmelweis UniversityBudapestHungary
  2. 2.1st Institute of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  3. 3.Hungarian Academy of SciencesMolecular Research GroupBudapestHungary

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