The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation

Abstract

The online version of this article has a Supplementary Appendix. BackgroundT follicular helper (TFH) cells reside in the light zone of germinal centers and are considered the cell of origin of angioimmunoblastic T-cell lymphoma. Recently, CXCL13, PD-1 and SAP were described as useful markers for TFH cells and angioimmunoblastic T-cell lymphoma but also reported in some peripheral T-cell lymphomas, not otherwise specified. Design and MethodsIn the present study the expression pattern of ICOS protein was investigated by immunohistochemistry-based techniques in routine sections of normal lymphoid tissues and 633 human lymphomas. ResultsCells strongly positive for ICOS were restricted to the light zone of germinal centers and co-expressed TFH-associated molecules. In addition, weak to moderate ICOS expression was observed in a small proportion of FOXP3-positive cells. In lymphomas, ICOS expression was confined to angioimmunoblastic T-cell lymphoma (85/86), peripheral T-cell lymphomas of follicular variant (18/18) and a proportion of peripheral T-cell lymphomas, not otherwise specified (24/56) that also expressed other TFH-associated molecules. ConclusionsICOS is a useful molecule for identifying TFH cells and its restricted expression to angioimmunoblastic T-cell lymphoma and a proportion of peripheral T-cell lymphomas, not otherwise specified (showing a TFH-like profile) suggests its inclusion in the antibody panel for diagnosing TFH-derived lymphomas. Our findings provide further evidence that the histological spectrum of TFH-derived lymphomas is broader than previously assumed. cell-derivation. Haematologica. 2010; 95:432-439. doi:10.3324/haematol.2009 This is an open-access paper. -cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation

Follicular center helper T-cell (TFH) marker positive mycosis fungoides/Sezary syndrome

“…13 These T cells are also known to express PD-1, CXCL-13, CD57, CXCR5, SAP, and ICOS with their differentiation controlled by Bcl-6. [14][15][16][17][18][19] Some T-cell lymphomas express follicular center helper T-cell markers including CD10, suggesting derivation from follicular center helper T cells. 15,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These include angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma with a follicular growth pattern, primary cutaneous CD4( þ ) small/ medium-sized pleomorphic T-cell lymphoma and, occasionally, peripheral T-cell lymphoma, not otherwise specified and anaplastic large cell lymphoma.…”

“…15,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These include angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma with a follicular growth pattern, primary cutaneous CD4( þ ) small/ medium-sized pleomorphic T-cell lymphoma and, occasionally, peripheral T-cell lymphoma, not otherwise specified and anaplastic large cell lymphoma. 15,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Clinically, primary cutaneous CD4( þ ) small/ medium-sized pleomorphic T-cell lymphoma and angioimmunoblastic T-cell lymphoma present or may present with primary cutaneous involvement. 20,[36][37][38][39][40] Other CD4( þ ) T-cell lymphomas with primary cutaneous manifestations include mycosis fungoides and its variants including Sezary syndrome, adult T-cell leukemia/lymphoma and primary cutaneous CD30 þ lymphoproliferative disorders.…”

CD10 and ICOS expression by multiparametric flow cytometry in angioimmunoblastic T-cell lymphoma

“…9,[14][15][16] More recently, the inducible T-cell costimulator (ICOS) protein has been proposed to be suitable for identifying T FH cells and to be perhaps superior to PD-1 for angioimmunoblastic T-cell lymphoma diagnosis. 17 Among T-cell lymphomas, ICOS expression analyzed by immunohistochemistry was indeed observed in angioimmunoblastic T-cell lymphoma (85/86 cases), and in the follicular variant of peripheral T-cell lymphoma, not otherwise specified (18/18 cases), a recently described variant of peripheral T-cell lymphoma showing phenotypic features in common with angioimmunoblastic T-cell lymphoma. 16,17 ICOS was also expressed by some peripheral T-cell lymphomas, not otherwise specified, showing a T FH -like profile (24/56).…”

“…17 Among T-cell lymphomas, ICOS expression analyzed by immunohistochemistry was indeed observed in angioimmunoblastic T-cell lymphoma (85/86 cases), and in the follicular variant of peripheral T-cell lymphoma, not otherwise specified (18/18 cases), a recently described variant of peripheral T-cell lymphoma showing phenotypic features in common with angioimmunoblastic T-cell lymphoma. 16,17 ICOS was also expressed by some peripheral T-cell lymphomas, not otherwise specified, showing a T FH -like profile (24/56). 17 Thus, ICOS appears rather as a diagnostic marker of T FH -derived lymphomas that encompass angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas, not otherwise specified, with some angioimmunoblastic T-cell lymphoma features.…”

Aspects moléculaires des lymphomes T périphériques (1)

“…Ces observations ont un intérêt pour le diagnostic et la classification. En effet, les marqueurs de TFH, CXCL13, PD1 ou ICOS, sont validés en tant que nouveaux biomarqueurs des LAIT et permettent en particulier de distinguer ce lymphome d'autres entités de LTP [17,18] (Figure 1). De façon intéressante, les mutations de TET2, DNMT3A, IDH2 sont également observées dans les hémopathies myéloïdes (non lymphoïdes) [33].…”