The role of immune checkpoint receptors in the malignant phenotype of cutaneous T cell lymphoma

Rony Shreberk-Hassidim, Anat Geiger-Maor, Galit Eisenberg, Sharon Merims, Emma Hajaj, Jonathan E. Cohen, Shiri Klein, Shoshana Frankenburg, Lilach Moyal, Emilia Hodak, Abraham Zlotogorski, Michal Lotem

Research output: Contribution to journalArticlepeer-review

Abstract

Immune checkpoint receptors (ICR) modulate the immune response and are critical hubs for immunotherapy. However, data on their role in T lymphoid malignancies, such as cutaneous T cell lymphoma (CTCL), is sparse. We aimed to explore the role of ICR in the malignant features of transformed T lymphocytes and evaluate the effect of ICR-targeting monoclonal antibodies, often used as immunotherapy for solid tumors. We used the CTCL cell line HH and the Sézary cell line Hut78 to examine ICR expression and the effects of ICR inhibition on cell viability and proliferation. Despite their shared T cell progeny, the different CTCL cell lines exhibit markedly different ICR expression profiles. Programmed cell death-ligand 1 (PD-L1) was expressed by both cell lines, while programmed death-1 (PD-1) was expressed only by the HH cell line. Common to all malignant T cells was an autonomous hyper-proliferative state that did not require T cell receptor stimulation. A monoclonal antibody blocking PD-1 had a small but statistically significant augmenting effect on T cell proliferation. Of note, when the cells were exposed to ionizing radiation, healthy lymphocytes and those derived from the HH cell line were salvaged by anti-PD-L1. We show a regulatory role of ICR, mainly PD-1 and its ligand PD-L1, on cutaneous T cell malignancy.

Original languageEnglish
JournalImmunologic Research
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Keywords

  • Cutaneous T cell lymphoma
  • Immune checkpoint receptors
  • Immunotherapy
  • Programmed death receptor ligand-1 (PDL-1)
  • Programmed death-1 (PD-1)

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