JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma.
Science
; 384(6702): eade8520, 2024 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38900864
ABSTRACT
Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti-PD-1 antibody nivolumab in Hodgkin lymphoma patients relapsed or refractory following checkpoint inhibitor immunotherapy. The combination yielded a best overall response rate of 53% (10/19). Ruxolitinib significantly reduced neutrophil-to-lymphocyte ratios and percentages of myeloid suppressor cells but increased numbers of cytokine-producing T cells. Ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade in preclinical solid tumor and lymphoma models. This synergy was characterized by a switch from suppressive to immunostimulatory myeloid cells, which enhanced T cell division.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazoles
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Pyrimidines
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Hodgkin Disease
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T-Lymphocytes
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Janus Kinase Inhibitors
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Nivolumab
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Immune Checkpoint Inhibitors
/
Nitriles
Limits:
Adult
/
Aged
/
Animals
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Science
Year:
2024
Document type:
Article