Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Lymphoma microenvironment: culprit or innocent?

Abstract

Studies are revealing that lymphoid neoplasms are characterized by well-defined chromosome translocations and by the accumulation of subsequent molecular alterations involving mainly the cell cycle and/or apoptotic pathways. However, survival of B and T tumor cells is also dependent on the interactions with the accompanying cells that comprise the lymphoma microenvironment. Although non-tumor cells can contribute both positive and negative signals to the lymphoma cells, in this review we present compelling evidence of the essential influence of the tumor microenvironment on the initiation and progression of specific lymphoma types, highlighting some new therapeutic approaches that target the lymphoma microenvironment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Sanchez-Beato M, Sanchez-Aguilera A, Piris MÁ . Cell cycle deregulation in B-cell lymphomas. Blood 2003; 101: 1220–1235.

    CAS  Google Scholar 

  2. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993; 342: 575–577.

    CAS  Google Scholar 

  3. Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002; 347: 89–94.

    CAS  Google Scholar 

  4. Sagaert X, De Wolf-Peeters C, Noels H, Baens M . The pathogenesis of MALT lymphomas: where do we stand? Leukemia 2007; 21: 389–396.

    CAS  Google Scholar 

  5. Nishio M, Endo T, Tsukada N, Ohata J, Kitada S, Reed JC et al. Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha. Blood 2005; 106: 1012–1020.

    CAS  Google Scholar 

  6. Tsukada N, Burger JA, Zvaifler NJ, Kipps TJ . Distinctive features of ‘nurselike’ cells that differentiate in the context of chronic lymphocytic leukemia. Blood 2002; 99: 1030–1037.

    CAS  Google Scholar 

  7. Schattner EJ, Mascarenhas J, Reyfman I, Koshy M, Woo C, Friedman SM et al. Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity. Blood 1998; 91: 2689–2697.

    CAS  Google Scholar 

  8. Lin-Lee YC, Pham LV, Tamayo AT, Fu L, Zhou HJ, Yoshimura LC et al. Nuclear localization in the biology of the CD40 receptor in normal and neoplastic human B lymphocytes. J Biol Chem 2006; 281: 18878–18887.

    CAS  Google Scholar 

  9. Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J et al. Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 2005; 11: 1467–1473.

    Google Scholar 

  10. Sanchez-Aguilera A, Montalban C, de la Cueva P, Sanchez-Verde L, Morente MM, Garcia-Cosio M et al. Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classical Hodgkin lymphoma. Blood 2006; 108: 662–668.

    CAS  Google Scholar 

  11. von Wasielewski R, Seth S, Franklin J, Fischer R, Hubner K, Hansmann ML et al. Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin's disease, allowing for known prognostic factors. Blood 2000; 95: 1207–1213.

    CAS  Google Scholar 

  12. Kuppers R . B cells under influence: transformation of B cells by Epstein–Barr virus. Nat Rev Immunol 2003; 3: 801–812.

    Google Scholar 

  13. de Leval L, Rickman DS, Thielen C, de Reynies A, Huang YL, Delsol G et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T cells (TFH). Blood 2007; 109: 4952–4963.

    CAS  Google Scholar 

  14. Carreras J, Lopez-Guillermo A, Fox BC, Colomo L, Martinez A, Roncador G et al. High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood 2006; 108: 2957–2964.

    CAS  Google Scholar 

  15. Eray M, Postila V, Eeva J, Ripatti A, Karjalainen-Lindsberg ML, Knuutila S et al. Follicular lymphoma cell lines, an in vitro model for antigenic selection and cytokine-mediated growth regulation of germinal centre B cells. Scand J Immunol 2003; 57: 545–555.

    CAS  Google Scholar 

  16. Farinha P, Masoudi H, Skinnider BF, Shumansky K, Spinelli JJ, Gill K et al. Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL). Blood 2005; 106: 2169–2174.

    CAS  Google Scholar 

  17. Hilchey SP, De A, Rimsza LM, Bankert RB, Bernstein SH . Follicular lymphoma intratumoral CD4+CD25+GITR+ regulatory T cells potently suppress CD3/CD28-costimulated autologous and allogeneic CD8+CD25− and CD4+CD25− T cells. J Immunol 2007; 178: 4051–4061.

    CAS  Google Scholar 

  18. Monti S, Savage KJ, Kutok JL, Feuerhake F, Kurtin P, Mihm M et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005; 105: 1851–1861.

    CAS  Google Scholar 

  19. Staudt LM, Dave S . The biology of human lymphoid malignancies revealed by gene expression profiling. Adv Immunol 2005; 87: 163–208.

    CAS  Google Scholar 

  20. Abramson JS . T-cell/histiocyte-rich B-cell lymphoma: biology, diagnosis, and management. Oncologist 2006; 11: 384–392.

    Google Scholar 

  21. Boudova L, Torlakovic E, Delabie J, Reimer P, Pfistner B, Wiedenmann S et al. Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood 2003; 102: 3753–3758.

    CAS  Google Scholar 

  22. Algara P, Mateo MS, Sanchez-Beato M, Mollejo M, Navas IC, Romero L et al. Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood 2002; 99: 1299–1304.

    CAS  Google Scholar 

  23. Bidegain F, Berry A, Alvarez M, Verhille O, Huguet F, Brousset P et al. Acute plasmodium falciparum malaria following splenectomy for suspected lymphoma in 2 patients. Clin Infect Dis 2005; 40: e97–e100.

    Google Scholar 

  24. Bates I, Bedu-Addo G . Chronic malaria and splenic lymphoma: clues to understanding lymphoma evolution. Leukemia 1997; 11: 2162–2167.

    CAS  Google Scholar 

  25. Wallace S, Bedu-Addo G, Rutherford TR, Bates I . Serological similarities between hyperreactive malarial splenomegaly and splenic lymphoma in west Africa. Trans R Soc Trop Med Hyg 1998; 92: 463–467.

    CAS  Google Scholar 

  26. Bates I, Bedu-Addo G, Jarrett RF, Schulz T, Wallace S, Armstrong A et al. B-lymphotropic viruses in a novel tropical splenic lymphoma. Br J Haematol 2001; 112: 161–166.

    CAS  Google Scholar 

  27. Hori S, Nomura T, Sakaguchi S . Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299: 1057–1061.

    CAS  Google Scholar 

  28. Bluestone JA, Abbas AK . Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3: 253–257.

    CAS  Google Scholar 

  29. Vinuesa CG, Tangye SG, Moser B, Mackay CR . Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 2005; 5: 853–865.

    CAS  Google Scholar 

  30. Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC . Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J Exp Med 2001; 193: 1373–1381.

    CAS  Google Scholar 

  31. Yu H, Kortylewski M, Pardoll D . Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007; 7: 41–51.

    CAS  Google Scholar 

  32. Kusmartsev S, Gabrilovich DI . STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 2005; 174: 4880–4891.

    CAS  Google Scholar 

  33. Alvaro T, Lejeune M, Camacho FI, Salvado MT, Sanchez L, Garcia JF et al. The presence of STAT1-positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma. Haematologica 2006; 91: 1605–1612.

    CAS  Google Scholar 

  34. Park CS, Choi YS . How do follicular dendritic cells interact intimately with B cells in the germinal centre? Immunology 2005; 114: 2–10.

    CAS  Google Scholar 

  35. Foucar K, Foucar E . The mononuclear phagocyte and immunoregulatory effector (M-PIRE) system: evolving concepts. Semin Diagn Pathol 1990; 7: 4–18.

    CAS  Google Scholar 

  36. Ingulli E, Mondino A, Khoruts A, Jenkins MK . In vivo detection of dendritic cell antigen presentation to CD4(+) T cells. J Exp Med 1997; 185: 2133–2141.

    CAS  Google Scholar 

  37. Liu YJ . IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 2005; 23: 275–306.

    CAS  Google Scholar 

  38. Kim R, Emi M, Tanabe K, Arihiro K . Potential functional role of plasmacytoid dendritic cells in cancer immunity. Immunology 2007; 121: 149–157.

    CAS  Google Scholar 

  39. Vacca A, Ribatti D . Bone marrow angiogenesis in multiple myeloma. Leukemia 2006; 20: 193–199.

    CAS  Google Scholar 

  40. Valent P, Schernthaner GH, Sperr WR, Fritsch G, Agis H, Willheim M et al. Variable expression of activation-linked surface antigens on human mast cells in health and disease. Immunol Rev 2001; 179: 74–81.

    CAS  Google Scholar 

  41. Weller PF . The immunobiology of eosinophils. N Engl J Med 1991; 324: 1110–1118.

    CAS  Google Scholar 

  42. Schubert LA, Jeffery E, Zhang Y, Ramsdell F, Ziegler SF . Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J Biol Chem 2001; 276: 37672–37679.

    CAS  Google Scholar 

  43. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY . Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005; 22: 329–341.

    CAS  Google Scholar 

  44. Singer KH, Scearce RM, Tuck DT, Whichard LP, Denning SM, Haynes BF . Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages. J Invest Dermatol 1989; 92: 166–170.

    CAS  Google Scholar 

  45. Lee IY, Ko EM, Kim SH, Jeoung DI, Choe J . Human follicular dendritic cells express prostacyclin synthase: a novel mechanism to control T cell numbers in the germinal center. J Immunol 2005; 175: 1658–1664.

    CAS  Google Scholar 

  46. Garnache-Ottou F, Feuillard J, Saas P . Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity? Br J Haematol 2007; 136: 539–548.

    CAS  Google Scholar 

  47. Stevenson FK, Caligaris-Cappio F . Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood 2004; 103: 4389–4395.

    CAS  Google Scholar 

  48. Burger M, Hartmann T, Krome M, Rawluk J, Tamamura H, Fujii N et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood 2005; 106: 1824–1830.

    CAS  Google Scholar 

  49. Haxhinasto SA, Bishop GA . Synergistic B cell activation by CD40 and the B cell antigen receptor: role of B lymphocyte antigen receptor-mediated kinase activation and tumor necrosis factor receptor-associated factor regulation. J Biol Chem 2004; 279: 2575–2582.

    CAS  Google Scholar 

  50. Ghia P, Circosta P, Scielzo C, Vallario A, Camporeale A, Granziero L et al. Differential effects on CLL cell survival exerted by different microenvironmental elements. Curr Top Microbiol Immunol 2005; 294: 135–145.

    CAS  Google Scholar 

  51. Kay NE, Wasil T . Survival of chronic lymphocytic leukemia cells: CD40L and the vascular endothelial growth factor (VEGF) connection. Leukemia 2005; 19: 531–532.

    CAS  Google Scholar 

  52. Balkwill F . Cancer and the chemokine network. Nat Rev Cancer 2004; 4: 540–550.

    CAS  Google Scholar 

  53. Stein JV, Nombela-Arrieta C . Chemokine control of lymphocyte trafficking: a general overview. Immunology 2005; 116: 1–12.

    CAS  Google Scholar 

  54. Burger JA, Burger M, Kipps TJ . Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 1999; 94: 3658–3667.

    CAS  Google Scholar 

  55. Redondo-Munoz J, Escobar-Diaz E, Samaniego R, Terol MJ, Garcia-Marco JA, Garcia-Pardo A . MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Blood 2006; 108: 3143–3151.

    CAS  Google Scholar 

  56. Burger JA, Kipps TJ . CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006; 107: 1761–1767.

    CAS  Google Scholar 

  57. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 2005; 201: 1307–1318.

    CAS  Google Scholar 

  58. Till KJ, Lin K, Zuzel M, Cawley JC . The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood 2002; 99: 2977–2984.

    CAS  Google Scholar 

  59. Kern C, Cornuel JF, Billard C, Tang R, Rouillard D, Stenou V et al. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood 2004; 103: 679–688.

    CAS  Google Scholar 

  60. Novak AJ, Bram RJ, Kay NE, Jelinek DF . Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival. Blood 2002; 100: 2973–2979.

    CAS  Google Scholar 

  61. Al-Saleem T, Al-Mondhiry H . Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms. Blood 2005; 105: 2274–2280.

    CAS  Google Scholar 

  62. Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 1999; 190: 1697–1710.

    CAS  Google Scholar 

  63. Batten M, Fletcher C, Ng LG, Groom J, Wheway J, Laabi Y et al. TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma. J Immunol 2004; 172: 812–822.

    CAS  Google Scholar 

  64. Planelles L, Carvalho-Pinto CE, Hardenberg G, Smaniotto S, Savino W, Gomez-Caro R et al. APRIL promotes B-1 cell-associated neoplasm. Cancer Cell 2004; 6: 399–408.

    CAS  Google Scholar 

  65. He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A . Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. J Immunol 2004; 172: 3268–3279.

    CAS  Google Scholar 

  66. Claudio E, Brown K, Park S, Wang H, Siebenlist U . BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat Immunol 2002; 3: 958–965.

    CAS  Google Scholar 

  67. Liao G, Zhang M, Harhaj EW, Sun SC . Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem 2004; 279: 26243–26250.

    CAS  Google Scholar 

  68. Woodland RT, Schmidt MR, Thompson CB . BLyS and B cell homeostasis. Semin Immunol 2006; 18: 318–326.

    CAS  Google Scholar 

  69. Ghia P, Caligaris-Cappio F . The indispensable role of microenvironment in the natural history of low-grade B-cell neoplasms. Adv Cancer Res 2000; 79: 157–173.

    CAS  Google Scholar 

  70. Johnson TA, Rassenti LZ, Kipps TJ . Ig VH1 genes expressed in B cell chronic lymphocytic leukemia exhibit distinctive molecular features. J Immunol 1997; 158: 235–246.

    CAS  Google Scholar 

  71. Rodriguez A, Villuendas R, Yanez L, Gomez ME, Diaz R, Pollan M et al. Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation. Leukemia 2007; 21: 1984–1991.

    CAS  Google Scholar 

  72. Chen L, Widhopf G, Huynh L, Rassenti L, Rai KR, Weiss A et al. Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood 2002; 100: 4609–4614.

    CAS  Google Scholar 

  73. Richardson SJ, Matthews C, Catherwood MA, Alexander HD, Carey BS, Farrugia J et al. ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B cell chronic lymphocytic leukaemia (B-CLL). Blood 2006; 107: 3584–3592.

    CAS  Google Scholar 

  74. Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 2007; 109: 729–739.

    CAS  Google Scholar 

  75. Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 2004; 103: 1755–1762.

    CAS  Google Scholar 

  76. Oudejans JJ, Jiwa NM, Kummer JA, Ossenkoppele GJ, van Heerde P, Baars JW et al. Activated cytotoxic T cells as prognostic marker in Hodgkin's disease. Blood 1997; 89: 1376–1382.

    CAS  Google Scholar 

  77. Poppema S, Visser L . Absence of HLA class I expression by Reed–Sternberg cells. Am J Pathol 1994; 145: 37–41.

    CAS  Google Scholar 

  78. Poppema S, van den Berg A . Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas. Semin Cancer Biol 2000; 10: 345–350.

    CAS  Google Scholar 

  79. Axdorph U, Porwit-MacDonald A, Grimfors G, Bjorkholm M . Tissue eosinophilia in relation to immunopathological and clinical characteristics in Hodgkin's disease. Leuk Lymphoma 2001; 42: 1055–1065.

    CAS  Google Scholar 

  80. Aldinucci D, Lorenzon D, Olivo K, Rapana B, Gattei V . Interactions between tissue fibroblasts in lymph nodes and Hodgkin/Reed-Sternberg cells. Leuk Lymphoma 2004; 45: 1731–1739.

    CAS  Google Scholar 

  81. Khnykin D, Troen G, Berner JM, Delabie J . The expression of fibroblast growth factors and their receptors in Hodgkin's lymphoma. J Pathol 2006; 208: 431–438.

    CAS  Google Scholar 

  82. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985; 66: 848–858.

    CAS  Google Scholar 

  83. Gruss HJ, Pinto A, Gloghini A, Wehnes E, Wright B, Boiani N et al. CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues. Am J Pathol 1996; 149: 469–481.

    CAS  Google Scholar 

  84. Lee SY, Lee SY, Kandala G, Liou ML, Liou HC, Choi Y . CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity. Proc Natl Acad Sci USA 1996; 93: 9699–9703.

    CAS  Google Scholar 

  85. Gedrich RW, Gilfillan MC, Duckett CS, Van Dongen JL, Thompson CB . CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins. J Biol Chem 1996; 271: 12852–12858.

    CAS  Google Scholar 

  86. Aizawa S, Nakano H, Ishida T, Horie R, Nagai M, Ito K et al. Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation. J Biol Chem 1997; 272: 2042–2045.

    CAS  Google Scholar 

  87. Duckett CS, Thompson CB . CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival. Genes Dev 1997; 11: 2810–2821.

    CAS  Google Scholar 

  88. Horie R, Aizawa S, Nagai M, Ito K, Higashihara M, Ishida T et al. A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation. Int Immunol 1998; 10: 203–210.

    CAS  Google Scholar 

  89. Horie R, Watanabe T, Morishita Y, Ito K, Ishida T, Kanegae Y et al. Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells. Oncogene 2002; 21: 2493–2503.

    CAS  Google Scholar 

  90. Vinante F, Rigo A, Scupoli MT, Pizzolo G . CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540. Blood 2002; 99: 52–60.

    CAS  Google Scholar 

  91. Biswas P, Mantelli B, Delfanti F, Ferrarini M, Poli G, Lazzarin A . CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes. Eur J Immunol 2003; 33: 3136–3145.

    CAS  Google Scholar 

  92. Fischer M, Harvima IT, Carvalho RF, Moller C, Naukkarinen A, Enblad G et al. Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. J Clin Invest 2006; 116: 2748–2756.

    CAS  Google Scholar 

  93. Hsu PL, Hsu SM . Autocrine growth regulation of CD30 ligand in CD30-expressing Reed-Sternberg cells: distinction between Hodgkin's disease and anaplastic large cell lymphoma. Lab Invest 2000; 80: 1111–1119.

    CAS  Google Scholar 

  94. Bechtel D, Kurth J, Unkel C, Kuppers R . Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 2005; 106: 4345–4350.

    CAS  Google Scholar 

  95. Re D, Kuppers R, Diehl V . Molecular pathogenesis of Hodgkin's lymphoma. J Clin Oncol 2005; 23: 6379–6386.

    CAS  Google Scholar 

  96. Grogg KL, Attygalle AD, Macon WR, Remstein ED, Kurtin PJ, Dogan A . Angioimmunoblastic T-cell lymphoma: a neoplasm of germinal-center T-helper cells? Blood 2005; 106: 1501–1502.

    CAS  Google Scholar 

  97. Irish JM, Czerwinski DK, Nolan GP, Levy R . Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells. Blood 2006; 108: 3135–3142.

    CAS  Google Scholar 

  98. Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004; 351: 2159–2169.

    CAS  Google Scholar 

  99. Corcione A, Ottonello L, Tortolina G, Facchetti P, Airoldi I, Guglielmino R et al. Stromal cell-derived factor-1 as a chemoattractant for follicular center lymphoma B cells. J Natl Cancer Inst 2000; 92: 628–635.

    CAS  Google Scholar 

  100. Husson H, Freedman AS, Cardoso AA, Schultze J, Munoz O, Strola G et al. CXCL13 (BCA-1) is produced by follicular lymphoma cells: role in the accumulation of malignant B cells. Br J Haematol 2002; 119: 492–495.

    CAS  Google Scholar 

  101. Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL, Aguiar RC et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002; 8: 68–74.

    CAS  Google Scholar 

  102. Hans CP, Weisenburger DD, Greiner TC, Chan WC, Aoun P, Cochran GT et al. Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol 2005; 18: 1377–1384.

    CAS  Google Scholar 

  103. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503–511.

    CAS  Google Scholar 

  104. Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM . A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA 2003; 100: 9991–9996.

    CAS  Google Scholar 

  105. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 1937–1947.

    Google Scholar 

  106. Savage KJ, Monti S, Kutok JL, Cattoretti G, Neuberg D, De Leval L et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003; 102: 3871–3879.

    CAS  Google Scholar 

  107. Traverse-Glehen A, Davi F, Ben Simon E, Callet-Bauchu E, Felman P, Baseggio L et al. Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection. Haematologica 2005; 90: 470–478.

    CAS  Google Scholar 

  108. Saadoun D, Suarez F, Lefrere F, Valensi F, Mariette X, Aouba A et al. Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity? Blood 2005; 105: 74–76.

    CAS  Google Scholar 

  109. Takeshita M, Sakai H, Okamura S, Oshiro Y, Higaki K, Nakashima O et al. Splenic large B-cell lymphoma in patients with hepatitis C virus infection. Hum Pathol 2005; 36: 878–885.

    CAS  Google Scholar 

  110. Ambrosetti A, Zanotti R, Pattaro C, Lenzi L, Chilosi M, Caramaschi P et al. Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection. Br J Haematol 2004; 126: 43–49.

    Google Scholar 

  111. Seve P, Renaudier P, Sasco AJ, Dumontet C, Salles G, Coiffier B et al. Hepatitis C virus infection and B-cell non-Hodgkin's lymphoma: a cross-sectional study in Lyon, France. Eur J Gastroenterol Hepatol 2004; 16: 1361–1365.

    Google Scholar 

  112. Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994; 330: 1267–1271.

    CAS  Google Scholar 

  113. Roggero E, Zucca E, Mainetti C, Bertoni F, Valsangiacomo C, Pedrinis E et al. Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin. Hum Pathol 2000; 31: 263–268.

    CAS  Google Scholar 

  114. Ferreri AJ, Ponzoni M, Guidoboni M, De Conciliis C, Resti AG, Mazzi B et al. Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol 2005; 23: 5067–5073.

    Google Scholar 

  115. Chanudet E, Zhou Y, Bacon C, Wotherspoon A, Muller-Hermelink HK, Adam P et al. Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J Pathol 2006; 209: 344–351.

    CAS  Google Scholar 

  116. Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004; 350: 239–248.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M A Piris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herreros, B., Sanchez-Aguilera, A. & Piris, M. Lymphoma microenvironment: culprit or innocent?. Leukemia 22, 49–58 (2008). https://doi.org/10.1038/sj.leu.2404970

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404970

Keywords

This article is cited by

Search

Quick links