Programmed death 1 is a marker of angioimmunoblastic T-Cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia

Department of Bio-pathology, Institut Paoli-Calmettes, Marseille 13009, France.
Human pathology (Impact Factor: 2.77). 08/2008; 39(7):1050-8. DOI: 10.1016/j.humpath.2007.11.012
Source: PubMed


Programmed death 1 (PD-1) is a lymphoid receptor that negatively regulates immune responses. PD-1 expression was recently reported in some T-cell non-Hodgkin lymphoma (NHL) subtypes, but the expression profile of PD-1 and its ligands (PD-L1 and PD-L2) in B-NHLs remains largely to be characterized. To investigate this issue, monoclonal antibodies against PD-1, PD-L1, and PD-L2 were generated by immunization of balb-c mice. A series of 161 lymphoma tissue and 11 blood samples was analyzed using either immunohistochemistry or flow cytometry. In reactive lymph nodes, PD-1 was mainly expressed in follicular T cells. In B-NHLs, PD-1 was mainly expressed in reactive T cells; but expression was also noted in neoplastic B cells from small lymphocytic lymphoma (SLL, 12/13), grade III follicular lymphoma (3/3), and diffuse large cell lymphoma (2/25). In contrast, neoplastic B cells from mantle cell lymphoma (0/11), marginal zone lymphoma (0/12), Burkitt lymphoma (0/3), and grade 1 to 2 follicular lymphoma (0/40) were PD-1 negative. PD-L1 and PD-L2 were negative in small B-cell lymphomas, including B-SLL. Flow cytometry showed that blood cells from chronic lymphocytic leukemia (B-CLL) also displayed PD-1 expression, which could be increased by CD40 stimulation. PD-1 expression in T-NHLs was restricted to the angioimmunoblastic subtype (8/8). These results show that PD-1 expression among B-NHLs is mainly associated with SLL/CLL and is influenced by activation of the CD40/CD40L pathway. Because the anti-PD-1.6.4 antibody works on paraffin sections, it represents a useful tool to differentiate SLL/CLL from other small B-cell lymphomas.

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    • "There is no PD-1 in mantle cell, marginal zone, Burkitt and I/II follicular lymphoma. PD-1 is mainly expressed in chronic lymphocytic leukemia/small B-cell lymphoma , which may be associated with the activation of CD40/CD40L pathway [19]. Our previous study found that TIM-3 level was increased in CD4+ and CD8+ T cells in DLBCL patients [20]. "
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    ABSTRACT: Objective: To investigate the expression of PD-1 and TIM-3 in CD3+ T cells in patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective analysis was conducted on data from 46 patients with newly diagnosed DLBCL and 30 healthy people. Flow cytometry was used to detect the expression of PD-1 and TIM-3 before and after chemotherapy. Results: Compared to healthy control, the expression of PD-1 and TIM-3 in patients with DLBCL was increased in CD3+ T cells. There is no significant change of PD-1 and TIM-3 in patients with stage I/II DLBCL, however, they were markedly increased in patients with stage III/IV DLBCL. The expression of PD-1 and TIM-3 elevated in DLBCL patients with B symptoms, IPI score >2 points and high level of LDH and Ki-67. After four courses of standard chemotherapy, PD-1 and TIM-3 expression level decreased. The treatment efficiency is higher in patients with low expression of PD-1 and TIM-3 than in patients with high PD-1 and TIM-3 expression. Conclusion: DLBCL patients have high expression level of PD-1 and TIM-3, which are related to DLBCL staging. PD-1 and TIM-3 expression levels are also related to the efficiency of chemotherapy. PD-1 and TIM-3 expression levels may be used as an indicator of chemotherapeutic efficacy in patients with DLBCL.
    Full-text · Article · Oct 2015
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    • "Down-regulation of Bcl-6 and CD10, which is frequently observed when neoplastic germinal center B-cells migrate out of the follicles in follicular lymphoma, has been observed in small numbers of FTCL cases reported [16] [19] [21]. It is important to remember that individual T FH markers can be expressed by other T-cell subsets, other types of T-cell lymphoma (eg, mycosis fungoides) and B-cell lymphoma (eg, chronic lymphocytic leukemia/small lymphocytic lymphoma) as well as in reactive conditions as reported by others [29] [30] [46] [50] [51] [53] [55] [57] [63] [65] [66] [67] [68] [69]. Therefore, it has been suggested that a combination of markers be used, with an arbitrary minimum of three markers being positive to define the T FH immunophenotype [29] [35] [54]. "
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    ABSTRACT: Unlike B-cell lymphomas, where knowledge of normal B-cell origin and differentiation has greatly contributed to their classification, the current classification of peripheral T-cell lymphomas is limited by a lack of understanding of their cellular origin. In the current World Health Organization classification of lymphomas, follicular T-cell lymphoma was formally recognized as a morphologic variant of peripheral T-cell lymphoma, not otherwise specified. There is growing evidence, however, that follicular T-cell lymphoma may be a unique clinicopathologic entity based on its morphologic features and derivation from follicular helper T-cells. In addition, there are abundant recent data supporting the concept that follicular helper T-cells can give rise to other types of T-cell lymphoma, including angioimmunoblastic T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoma, and a subset of neoplasms, in addition to follicular T-cell lymphoma, currently classified as peripheral T-cell lymphoma, not otherwise specified. In this review, we focus primarily on the clinicopathologic, immunophenotypic, and molecular features of follicular T-cell lymphoma and discuss its potential relationship with other types of T-cell lymphoma thought to be derived from follicular helper T-cells.
    Full-text · Article · Sep 2012 · Human pathology
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    • "Expression of PD-1 was found on tumor infiltrating and peripheral T cells in Hodgkin lymphoma, B-cell non-Hodgkin lymphoma as well as in the adult T-cell leukemia [19], [20], [21], [22]. PD-1 was described also as a marker of T cells associated with germinal centers and as a marker of angioimmunoblastic T-cell lymphoma [19], [23], [24]. Among B-cell non-Hodgkin lymphomas, PD-1 presence was described on 3 of 98 cases of diffuse large B-cell lymphomas (DLBCL), 12 of 13 cases of small lymphocytic lymphoma and 10 of 11 cases of CLL [23], [24]. "
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    ABSTRACT: Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies.
    Full-text · Article · Apr 2012 · PLoS ONE
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