Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells

Shaffer AL, Rosenwald A, Staudt LM . Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2002; 2: 920–932.

Thomazy VA, Vega F, Medeiros LJ, Davies PJ, Jones D . Phenotypic modulation of the stromal reticular network in normal and neoplastic lymph nodes: tissue transglutaminase reveals coordinate regulation of multiple cell types. Am J Pathol 2003; 163: 165–174.

Carbone A, Gloghini A, Gruss HJ, Pinto A . CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease. Am J Pathol 1995; 147: 912–922.

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.

Glas AM, Knoops L, Delahaye L, Kersten MJ, Kibbelaar RE, Wessels LA et al. Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma. J Clin Oncol 2007; 25: 390–398.

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.

Farinha P, Al-Tourah A, Gill K, Klasa R, Connors JM, Gascoyne RD . The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation. Blood 2010; 115: 289–295.

Yang ZZ, Grote DM, Ziesmer SC, Manske MK, Witzig TE, Novak AJ et al. Soluble IL-2R{alpha} facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood 2011; 118: 2809–2820.

Yang ZZ, Novak AJ, Stenson MJ, Witzig TE, Ansell SM . Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood 2006; 107: 3639–3646.

Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, Ansell SM . Attenuation of CD8(+) T-cell function by CD4(+)CD25(+) regulatory T cells in B-cell non-Hodgkin's lymphoma. Cancer Res 2006; 66: 10145–10152.

Alvaro T, Lejeune M, Salvado MT, Lopez C, Jaen J, Bosch R et al. Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients. J Clin Oncol 2006; 24: 5350–5357.

Carreras J, Lopez-Guillermo A, Roncador G, Villamor N, Colomo L, Martinez A et al. High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma. J Clin Oncol 2009; 27: 1470–1476.

Richendollar BG, Pohlman B, Elson P, Hsi ED . Follicular programmed death 1-positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma. Hum Pathol 2011; 42: 552–557.

Crotty S . Follicular Helper CD4T Cells (T(FH)). Annu Rev Immunol 2011; 29: 621–663.

Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009; 325: 1006–1010.

Ma CS, Suryani S, Avery DT, Chan A, Nanan R, Santner-Nanan B et al. Early commitment of naive human CD4(+) T cells to the T follicular helper (T(FH)) cell lineage is induced by IL-12. Immunol Cell Biol 2009; 87: 590–600.

Pangault C, Ame-Thomas P, Ruminy P, Rossille D, Caron G, Baia M et al. Follicular lymphoma cell niche: identification of a preeminent IL-4-dependent T(FH)-B cell axis. Leukemia 2010; 24: 2080–2089.

Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 2009; 10: 167–175.

Akiba H, Takeda K, Kojima Y, Usui Y, Harada N, Yamazaki T et al. The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J Immunol 2005; 175: 2340–2348.

Rasheed AU, Rahn HP, Sallusto F, Lipp M, Muller G . Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4T cells and is independent of CD57 expression. Eur J Immunol 2006; 36: 1892–1903.

Marinova E, Han S, Zheng B . Germinal center helper T cells are dual functional regulatory cells with suppressive activity to conventional CD4+ T cells. J Immunol 2007; 178: 5010–5017.

Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, Bover L et al. Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 2008; 28: 870–880.

Maby-El Hajjami H, Ame-Thomas P, Pangault C, Tribut O, DeVos J, Jean R et al. Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine-2,3 dioxygenase. Cancer Res 2009; 69: 3228–3237.

Pene J, Chevalier S, Preisser L, Venereau E, Guilleux MH, Ghannam S et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 2008; 180: 7423–7430.

Hamalainen HK, Tubman JC, Vikman S, Kyrola T, Ylikoski E, Warrington JA et al. Identification and validation of endogenous reference genes for expression profiling of T helper cell differentiation by quantitative real-time RT-PCR. Anal Biochem 2001; 299: 63–70.

Bruneau J, Canioni D, Renand A, Marafioti T, Paterson JC, Martin-Garcia N et al. Regulatory T-cell depletion in angioimmunoblastic T-cell lymphoma. Am J Pathol 2010; 177: 570–574.

Yssel H, De Vries JE, Koken M, Van Blitterswijk W, Spits H . Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods 1984; 72: 219–227.

Deenick EK, Chan A, Ma CS, Gatto D, Schwartzberg PL, Brink R et al. Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 2010; 33: 241–253.

Reinhardt RL, Liang HE, Locksley RM . Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 2009; 10: 385–393.

Manches O, Lui G, Chaperot L, Gressin R, Molens JP, Jacob MC et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 2003; 101: 949–954.

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.

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.

de Jong D, de Boer JP . Predicting transformation in follicular lymphoma. Leuk Lymphoma 2009; 50: 1406–1411.

Strauss L, Bergmann C, Szczepanski MJ, Lang S, Kirkwood JM, Whiteside TL . Expression of ICOS on human melanoma-infiltrating CD4+CD25highFoxp3+ T regulatory cells: implications and impact on tumor-mediated immune suppression. J Immunol 2008; 180: 2967–2980.

Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, Ansell SM . CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25T cells. Blood 2007; 110: 2537–2544.

Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, Ansell SM . Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin's lymphoma. Cancer Res 2009; 69: 5522–5530.

Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF et al. Foxp3(+) follicular regulatory T cells control the germinal center response. Nat Med 2011; 17: 975–982.

Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med 2011; 17: 983–988.

Lim HW, Kim CH . Loss of IL-7 receptor alpha on CD4+ T cells defines terminally differentiated B cell-helping effector T cells in a B cell-rich lymphoid tissue. J Immunol 2007; 179: 7448–7456.

Ame-Thomas P, Maby-El Hajjami H, Monvoisin C, Jean R, Monnier D, Caulet-Maugendre S et al. Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood 2007; 109: 693–702.

Byers RJ, Sakhinia E, Joseph P, Glennie C, Hoyland JA, Menasce LP et al. Clinical quantitation of immune signature in follicular lymphoma by RT-PCR-based gene expression profiling. Blood 2008; 111: 4764–4770.

Clear AJ, Lee AM, Calaminici M, Ramsay AG, Morris KJ, Hallam S et al. Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment. Blood 2010; 115: 5053–5056.

Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A et al. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol 2010; 11: 846–853.

Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 2008; 453: 65–71.

Ramirez JM, Brembilla NC, Sorg O, Chicheportiche R, Matthes T, Dayer JM et al. Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. Eur J Immunol 2010; 40: 2450–2459.

Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D et al. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol 2010; 11: 854–861.

Illera VA, Perandones CE, Stunz LL, Mower Jr DA, Ashman RF . Apoptosis in splenic B lymphocytes. Regulation by protein kinase C and IL-4. J Immunol 1993; 151: 2965–2973.

Wurster AL, Rodgers VL, White MF, Rothstein TL, Grusby MJ . Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL. J Biol Chem 2002; 277: 27169–27175.

Sarosiek KA, Nechushtan H, Lu X, Rosenblatt JD, Lossos IS . Interleukin-4 distinctively modifies responses of germinal centre-like and activated B-cell-like diffuse large B-cell lymphomas to immuno-chemotherapy. Br J Haematol 2009; 147: 308–318.

Schmitter D, Koss M, Niederer E, Stahel RA, Pichert G . T-cell derived cytokines co-stimulate proliferation of CD40-activated germinal centre as well as follicular lymphoma cells. Hematol Oncol 1997; 15: 197–207.

Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 2010; 24: 241–255.