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Peripheral T cell lymphomas: from the bench to the clinic

Nature Reviews Cancer volume 20, pages 323–342 (2020)Cite this article

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Abstract

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of orphan neoplasms. Despite the introduction of anthracycline-based chemotherapy protocols, with or without autologous haematopoietic transplantation and a plethora of new agents, the progression-free survival of patients with PTCLs needs to be improved. The rarity of these neoplasms, the limited knowledge of their driving defects and the lack of experimental models have impaired clinical successes. This scenario is now rapidly changing with the discovery of a spectrum of genomic defects that hijack essential signalling pathways and foster T cell transformation. This knowledge has led to new genomic-based stratifications, which are being used to establish objective diagnostic criteria, more effective risk assessment and target-based interventions. The integration of genomic and functional data has provided the basis for targeted therapies and immunological approaches that underlie individual tumour vulnerabilities. Fortunately, novel therapeutic strategies can now be rapidly tested in preclinical models and effectively translated to the clinic by means of well-designed clinical trials. We believe that by combining new targeted agents with immune regulators and chimeric antigen receptor-expressing natural killer and T cells, the overall survival of patients with PTCLs will dramatically increase.

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Fig. 1: Classification and ethnic and geographic distribution of most recurrent T cell lymphoproliferative disorders.
Fig. 2: Transcription factors regulate the phenotype and function of T cells.
Fig. 3: The mechanisms of PTCL transformation.
Fig. 4: Dysregulated signalling pathways in PTCL.
Fig. 5: Clonal haematopoiesis and T cell lymphoma of follicular helper cell origin.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA

    Danilo Fiore, Luca Vincenzo Cappelli & Giorgio Inghirami

  2. Department of Translational and Precision Medicine, Sapienza University, Rome, Italy

    Luca Vincenzo Cappelli

  3. Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy

    Alessandro Broccoli & Pier Luigi Zinzani

  4. Department of Pathology, City of Hope Medical Center, Duarte, CA, USA

    Wing C. Chan

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  1. Danilo Fiore
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  4. Pier Luigi Zinzani
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A cytokine produced by immune cells. Lymphokines have an array of properties regulating cell activation, growth, migration and survival.

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The process whereby T cells recognize antigens presented by professional antigen-presenting cells (that is, macrophages and dendritic cells) via the T cell receptor complex and then undergo activation in the presence of effective co-stimulatory signals, initiating antigen-specific adaptive immune responses.

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On-target/off-tumour effect

A drug-mediated or cell-mediated on-target/off-tumour effect leads to undesirable toxicity caused by the expression of the targeted protein or antigen on normal cells.

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Fiore, D., Cappelli, L.V., Broccoli, A. et al. Peripheral T cell lymphomas: from the bench to the clinic. Nat Rev Cancer 20, 323–342 (2020). https://doi.org/10.1038/s41568-020-0247-0

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