Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.
Science
; 384(6702): eadf1329, 2024 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-38900877
ABSTRACT
Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Linfócitos T CD8-Positivos
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Janus Quinase 1
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Receptor de Morte Celular Programada 1
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Inibidores de Janus Quinases
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Inibidores de Checkpoint Imunológico
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Neoplasias Pulmonares
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos