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

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

Journal

Immunologic research
ISSN: 1559-0755
Titre abrégé: Immunol Res
Pays: United States
ID NLM: 8611087

Informations de publication

Date de publication:
12 2022
Historique:
received: 28 02 2022
accepted: 13 07 2022
pubmed: 23 7 2022
medline: 16 11 2022
entrez: 22 7 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35867216
doi: 10.1007/s12026-022-09308-6
pii: 10.1007/s12026-022-09308-6
doi:

Substances chimiques

Programmed Cell Death 1 Receptor 0
B7-H1 Antigen 0
Ligands 0
Antibodies, Monoclonal 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

793-799

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Rony Shreberk-Hassidim (R)

Department of Dermatology, The Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel. rshreberk@gmail.com.

Anat Geiger-Maor (A)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Galit Eisenberg (G)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Sharon Merims (S)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Emma Hajaj (E)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Jonathan E Cohen (JE)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
The Wohl Institute for Translational Medicine, Hadassah Medical Center, Jerusalem, Israel.

Shiri Klein (S)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Shoshana Frankenburg (S)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Lilach Moyal (L)

Department of Dermatology, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Emilia Hodak (E)

Department of Dermatology, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abraham Zlotogorski (A)

Department of Dermatology, The Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Michal Lotem (M)

The Faculty of Medicine, Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

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