Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers

Abstract

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 subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs. Results Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01). Conclusion Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

Anti–PD-1 chimeric antigen receptor T cells efficiently target SIV-infected CD4+ T cells in germinal centers

“…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 – 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.…”

Benefit of prednisolone alone in nodal peripheral T-cell lymphoma with T follicular helper phenotype

“…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.…”