The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.
immune checkpoint inhibitor
immune evasion
immune regulation
interferon gamma
Journal
Essays in biochemistry
ISSN: 1744-1358
Titre abrégé: Essays Biochem
Pays: England
ID NLM: 0043306
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
31
03
2023
revised:
26
06
2023
accepted:
27
06
2023
pubmed:
28
7
2023
medline:
28
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy. Here, we highlight the paradoxical role of the cytokine interferon-γ (IFN-γ) in ICBT response: on the one hand induction of IFN-γ signalling in the tumour microenvironment correlates with good ICBT response as it drives the cellular immune responses required for tumour destruction; nonetheless, IFN-γ signalling is implicated in ICBT acquired resistance. We address the negative feedback and immunoregulatory effects of IFN-γ signalling that promote immune evasion and resistance to ICBT and discuss how these can be targeted pharmacologically to restore sensitivity or circumvent resistance.
Identifiants
pubmed: 37503572
pii: 233326
doi: 10.1042/EBC20230001
pmc: PMC10539948
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
991-1002Informations de copyright
© 2023 The Author(s).
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