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Open Access 25-03-2024 | Solid Tumor | REVIEW

OX40/OX40 ligand and its role in precision immune oncology

Authors: Bicky Thapa, Shumei Kato, Daisuke Nishizaki, Hirotaka Miyashita, Suzanna Lee, Mary K. Nesline, Rebecca A. Previs, Jeffery M. Conroy, Paul DePietro, Sarabjot Pabla, Razelle Kurzrock

Published in: Cancer and Metastasis Reviews

Abstract

Immune checkpoint inhibitors have changed the treatment landscape for various malignancies; however, their benefit is limited to a subset of patients. The immune machinery includes both mediators of suppression/immune evasion, such as PD-1, PD-L1, CTLA-4, and LAG-3, all of which can be inhibited by specific antibodies, and immune-stimulatory molecules, such as T-cell co-stimulatory receptors that belong to the tumor necrosis factor receptor superfamily (TNFRSF), including OX40 receptor (CD134; TNFRSF4), 4-1BB (CD137; TNFRSF9), and glucocorticoid-induced TNFR-related (GITR) protein (CD357; TNFRSF18). In particular, OX40 and its binding ligand OX40L (CD134L; TNFSF4; CD252) are critical for immunoregulation. When OX40 on activated T cells binds OX40L on antigen-presenting cells, T-cell activation and immune stimulation are initiated via enhanced T-cell survival, proliferation and cytotoxicity, memory T-cell formation, and abrogation of regulatory T cell (Treg) immunosuppressive functions. OX40 agonists are in clinical trials both as monotherapy and in combination with other immunotherapy agents, in particular specific checkpoint inhibitors, for cancer treatment. To date, however, only a minority of patients respond. Transcriptomic profiling reveals that OX40 and OX40L expression vary between and within tumor types, and that only ~ 17% of cancer patients have high OX40 and low OX40L, one of the expression patterns that might be theoretically amenable to OX40 agonist enhancement. Taken together, the data suggest that the OX40/OX40L machinery is a critical part of the immune stimulatory system and that understanding endogenous expression patterns of these molecules and co-existing checkpoints merits further investigation in the context of a precision immunotherapy strategy for cancer therapy.

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Title: OX40/OX40 ligand and its role in precision immune oncology
Authors: Bicky Thapa
Shumei Kato
Daisuke Nishizaki
Hirotaka Miyashita
Suzanna Lee
Mary K. Nesline
Rebecca A. Previs
Jeffery M. Conroy
Paul DePietro
Sarabjot Pabla
Razelle Kurzrock
Publication date: 25-03-2024
Publisher: Springer US
Keyword: Solid Tumor
Published in: Cancer and Metastasis Reviews
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-024-10184-9

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer