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.
"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   . 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              . 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   . "
[Show abstract][Hide abstract] 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.
Human pathology 09/2012; 43(11):1789-98. DOI:10.1016/j.humpath.2012.05.002 · 2.77 Impact Factor
"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 , , , . PD-1 was described also as a marker of T cells associated with germinal centers and as a marker of angioimmunoblastic T-cell lymphoma , , . 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 , . "
[Show abstract][Hide abstract] 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.
PLoS ONE 04/2012; 7(4):e35178. DOI:10.1371/journal.pone.0035178 · 3.23 Impact Factor
"Genes overexpressed in H/TCRBCL belonged to functional categories including genes related to macrophages (STAT1, LAMP1) and Th1 response (IFNG, CCR5) . One of the most significantly overrepresented genes in H/TCRBCL was PDCD1/PD-1, which codes for a lymphocyte inhibitory receptor expressed in specific lymphoma subtypes . PD-1 protein expression was validated using IHC in 130 cHL and 13 H/TCRBCL. "
[Show abstract][Hide abstract] ABSTRACT: Gene expression profiling studies based on DNA microarrays have demonstrated their ability to define the interaction pathways between neoplastic and nonmalignant stromal cells in cancer tissues. During the past ten years, a number of approaches including microdissection have tried to resolve the variability in DNA microarray measurements stemming from cancer tissue sample heterogeneity. Another approach, designated as virtual or in silico microdissection, avoids the laborious and time-consuming step of anatomic microdissection. It consists of confronting the gene expression profiles of complex tissue samples to those of cell lines representative of different cell lineages, different differentiation stages, or different signaling pathways. This strategy has been used in recent studies aiming to analyze microenvironment alterations using gene expression profiling of nonmicrodissected classical Hodgkin lymphoma tissues in order to generate new prognostic factors. These recent contributions are detailed and discussed in the present paper.
Advances in Hematology 01/2011; 2011:485310. DOI:10.1155/2011/485310
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