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The effect of imatinib on T and B cells in patients with chronic myelogenous leukaemia (CML) is not well understood. An upregulation of the transcription factor Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar 1 bZip transcription factor 2 (BACH2), which is involved in the development and differentiation of B cells, was demonstrated in a CML cell line treated with imatinib. The present study retrospectively analysed the expression and distribution of cluster of differentiation (CD)3, CD20 and BACH2 (per 1,000 cells), as well as the co-expression of CD20 and BACH2, using immunohistochemistry in serial bone marrow trephines obtained from 14 CML patients treated with imatinib in comparison to 17 patients with newly diagnosed CML and 6 control trephines. Bone marrow trephines of CML patients in remission under imatinib therapy exhibited significantly higher numbers of CD3 and CD20 infiltrates (partly ordered in aggregates) compared with patients with newly diagnosed CML and control individuals. Similarly, nuclear expression of BACH2 in granulopoietic cells was increased in CML patients treated with imatinib, which may represent the histological correlate of the positive treatment effect. Furthermore, since BACH2 is involved in B cell development, its altered expression patterns by imatinib may be one explanation for high B cell numbers, as revealed by CD20/BACH2 (nuclear)-positive cells. As the present data are preliminary, future prospective studies are required to assess the prognostic and predictive role of BACH2 in patients with CML under targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: Infection with Toxoplasma gondii (TG) presents in some individuals as a self-limited disease with a predominant lymphadenopathy characterized by prominent B-cell activation. As this is in contrast to the in vitro based concept of a Th1-immune response against TG, we investigated native lymphoid tissue and peripheral blood of a patient with serologic evidence of toxoplasmosis to verify which cells show Th1-response features. High-level expression of T-bet in monocytoid B-cells, in germinal center B-cells, and in a lesser amount in T cells could be demonstrated by immunohistochemistry. In vitro stimulation of lymph node cells with either TG, staphylococcus enterotoxin B, or phorbol 12-myristate 13-acetate/ionomycin revealed an interferon-γ expression in T-bet+ B cells only in the patient and not in controls. Similar results were found for T-bet+ T cells which were also present in controls. CD4+ peripheral blood cells stimulated with TG antigens showed a TG-specific but attenuated Th1-reactivity in the patient associated with a reduced expression of IL-2 when compared with controls. We conclude that the pathogenesis and course of toxoplasmic lymphadenopathy is based on a Th1-cell defect, which becomes compensated by the B cells mounting a Th1-like immune response. [Copyright &y& Elsevier]

Hairy cell leukemia (HCL) is an uncommon B-cell malignancy with unknown pathogenesis. In an earlier study, we demonstrated that HCL cells highly express the transcription factor T-box-expressed-in-T-cells (T-bet). T-bet is the master regulator of the T-helper (Th)1 cell response regulating interferon gamma (IFN-γ) production and also plays a central role in the T-cell independent Th1-like B-cell response. Here, we demonstrate by fluorescence activated cell sorting (FACS) analysis that neoplastic cells from the peripheral blood of five patients with HCL showed an enhanced expression of IFN-γ after stimulation. Additionally, a comparison with 55 healthy individuals revealed a significant elevation of IFN-γ in the sera of patients with HCL. Based on our recent findings that a non-neoplastic B-cell subset, the monocytoid B-cells, are T-bet positive and produce IFN-γ, we propose that monocytoid and hairy B-cells have a similar function and that the T-bet-IFN-γ axis is involved in the pathogenesis of HCL. [ABSTRACT FROM AUTHOR]

Stein H, Jöhrens K, Anagnostopoulos I. Non-mediastinal grey zone lymphomas and report from the workshop.Eur J Haematol 2005: 75 (Suppl. 66): 42–44.© Blackwell Munksgaard 2005.Grey zone lymphomas represent borderline lesions between classical Hodgkin lymphoma (cHL) and other morphologically and immunophenotypically related diseases and entities like nodular lymphocyte predominant HL, T-cell rich B-cell lymphoma, ALK-negative anaplastic large cell lymphoma (ALCL), diffuse large B cell lymphoma (DLBCL) anaplastic variant and primary mediastinal LBCL. The sharp definition of morphological, immunophenotypical and molecular features of the‘‘text-book cases’’ of each disease and the comparison with grey zone cases has reduced most of the latter cases. Two reports in this workshop dealt with the problematic non-mediastinal grey zone lymphomas, one with a cHL of T cell-type presenting in the skin as a ALK-negative ALCL and the other with the grey zone between cHL of B-cell type and ALK-negative ALCL. [ABSTRACT FROM AUTHOR]

To date, most studies investigating the immune tumor microenvironment of non-small cell lung cancers (NSCLC) only consider a small number of immune cell subsets or do not reflect the distribution of these cells between different tumor compartments as they were performed on tissue microarrays (TMA). To address this, we analyzed the immune infiltrate in surgically resected NSCLCs, focusing on potential spatial heterogeneity. We evaluated 45 NSCLCs based on whole-slide sections using immunohistochemistry with eleven different antibodies (CD3, CD4, CD8, CD20, CD68, Gata3, FOXP3, T-bet, kappa, lambda, PD-L1). While most markers were relatively evenly distributed among different tumor compartments as well as within the same tumor compartment, some immune cell subsets showed a considerable variance. Notably, the immune infiltrate at the tumor invasion front was dominated by B cells. Concerning markers for T cell differentiation, FoxP3 (Th2) was predominantly expressed in stromal lymphocytes, while T-bet (Th1) was most commonly expressed in intraepithelial immune cells. Although most immune cell subtypes showed a heterogenous distribution within in the intraepithelial compartment, the results from a simulated TMA and core biopsy were mostly in line with the results from whole slide evaluation. Regarding disease specific survival, there were no clear correlations. Interestingly, patients with intraepithelial T-bet positive lymphocytes had a significantly better outcome (p = 0.039), however, this difference was not preserved in multivariate analysis. In conclusion, our study shows that the immune tumor microenvironment of NSCLCs is complex and partially heterogenous, especially concerning markers for T cell differentiation. [ABSTRACT FROM AUTHOR]