Fig 2 - available from: Diagnostic Pathology
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Immunohistological findings of patients with large cell PTCL-TFH. Atypical large lymphoid cells are diffusely positive for PD-1 (a), CXCL13 (b), CMYC (c) and PD-L1 (d). PD-L1+ tumour cells, dendritic and histiocytic cells are admixed. Magnification, × 400
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Background
The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated.
Methods
Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassifie...
Contexts in source publication
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... cell PTCL-TFH patients had significantly lower populations of clear neoplastic cells and fewer reactions of eosinophils and plasma cells than those of AITL ( Fig. 1a, b; both p < 0.01). Large cell PTCL-TFH expressed more than two TFH markers; among them PD-1 was positive in 12 patients (92%; Fig. 2a), BCL6 in 12 (92%), CXCL13 in seven (54%; Fig. 2b) and CD10 in seven (54%). Small cell PTCL-TFH showed frequent expressions of PD-1 (100%) and BCL6 (89%), but rarely of CD10 (11%). Four of 10 Lennert lymphoma patients showed more than two TFH markers (Fig. 1c, f). Large cell PTCL-TFH showed frequent expression of CD25 in eight patients ...
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... cell PTCL-TFH patients had significantly lower populations of clear neoplastic cells and fewer reactions of eosinophils and plasma cells than those of AITL ( Fig. 1a, b; both p < 0.01). Large cell PTCL-TFH expressed more than two TFH markers; among them PD-1 was positive in 12 patients (92%; Fig. 2a), BCL6 in 12 (92%), CXCL13 in seven (54%; Fig. 2b) and CD10 in seven (54%). Small cell PTCL-TFH showed frequent expressions of PD-1 (100%) and BCL6 (89%), but rarely of CD10 (11%). Four of 10 Lennert lymphoma patients showed more than two TFH markers (Fig. 1c, f). Large cell PTCL-TFH showed frequent expression of CD25 in eight patients (62%) and CD30 in five (39%; Fig. 1d, e), which ...
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... higher than one (11%) and 0 (0%), respectively, in small cell PTCL-TFH, and eight (21%) and one (4%), respectively, in AITL (p < 0.05, p < 0.01, respectively). Scattered and patchy infiltrates of CD30+ lymphoma cells were detected in the five large cell PTCL-TFH patients. Large cell PTCL-TFH was frequently positive for CMYC in 10 patients (77%, Fig. 2c) and MIB1 in 13 (100%), which were significantly higher than 0 (0%) and seven (78%), respectively, in small cell PTCL-TFH, and 12 (31%) and 29 (74%), respectively, in AITL (p < 0.05, p < 0.01, respectively). Mean CMYC mRNA was 4.1 in tumour specimens of 42 patients, and ≥ 4.1 CMYC mRNA was detected in six of seven large cell PTCL-TFH ...
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... (86%), which was significantly higher than in small cell PTCL-TFH (0/5, 0%) and F-TCL (0/5, 0%) (both p < 0.05). The combination of PD-L1+ tumour cells and intense reaction (R3+) of PD-L1+ non-neoplastic cells (high PD-L1+ group) was found in eight large cell PTCL-TFH patients (62%), which was significantly higher than in F-TCL (0%) (p = 0.036; Fig. 2d). Scattered EBERs+ lymphocytes in the background were found in large cell (92%) and small cell (89%) PTCL-TFH patients, compared with large cell (29%) and small cell (56%) PTCL-NOS groups (p < 0.01, p < 0.05, ...
Citations
... As CAR T cells are increasingly explored in multiple disease indications (55), a second generation anti-PD-1 CAR approach could be considered in oncology to treat selective PD-1-expressing tumors such as angioimmunoblastic T cell lymphoma (56)(57)(58)(59) and nodal peripheral T cell lymphomas with TFH markers (60). Another application of anti-PD-1 CAR T cells could be in the treatment of autoimmune diseases. ...
Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4⁺ T cells. We engineered an anti–PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239–infected rhesus macaques (RMs). Adoptive transfer of anti–PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti–PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1⁺ memory T cells in blood and tissues, including lymph node CD4⁺ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8⁺ memory T cells. These data indicate anti–PD-1 CAR T cells depleted PD-1⁺ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.
... 5,6 There are no large studies exclusively on the clinical characteristics of nodal PTCL with TFH phenotype (since this case was diagnosed before WHO-HAEM5 and ICC-2022 were published, we use this pathological diagnosis hereafter); however, like AITL, it is considered to be a clinically aggressive disease. [7][8][9] A few scattered case reports have reported that a subset of newly diagnosed or relapsed patients with AITL or FTCL responded to immunosuppressive therapies such as prednisolone (PSL) and/or cyclosporin A (CsA). [10][11][12][13] However, to the best of our knowledge, there are no reports on patients with nodal PTCL with TFH phenotype who responded to immunosuppressive therapies. ...
A 71-year-old Japanese man presented with severe thrombocytopenia. A whole-body CT at presentation showed small cervical, axillary, and para-aortic lymphadenopathy, leading to suspicion of immune thrombocytopenia due to lymphoma. Biopsy was difficult to perform because of severe thrombocytopenia. Thus, he received prednisolone (PSL) therapy and his platelet count gradually recovered. Two and a half years after PSL therapy initiation, his cervical lymphadenopathy slightly progressed without other clinical symptoms. Hence, a biopsy from the left cervical lymph node was performed, and he was diagnosed with nodal peripheral T-cell lymphoma (PTCL) with T follicular helper (TFH) phenotype. Due to various complications, we continued treatment with prednisolone alone after the diagnosis of lymphoma; however, there was no further increase in lymph node enlargement and no other lymphoma-related symptoms for one and a half years after diagnosis. Although immunosuppressive therapy has been reported to produce a response in some patients with angioimmunoblastic T-cell lymphoma, our experience suggests that a similar subset may exist in patients with nodal PTCL with TFH phenotype, which has the same cellular origin. Immunosuppressive therapies may constitute an alternative treatment option even in the era of novel molecular-targeted therapies, especially for elderly patients who are ineligible for chemotherapy.
