JCI - Single-cell characterization of anti-LAG3+anti-PD1 treatment in melanoma patients

Scientists unravel the effects of new medication for advanced melanoma with the help of AI jclinicalinvest

-line therapy in stage III/IV melanoma, but its detailed effect on the immune system is unknown.We evaluated blood samples from 40 immunotherapy-naïve or prior immunotherapy-refractory patients with metastatic melanoma treated with anti-LAG3+anti-PD1 in a phase I trial using single-cell RNA and T cell receptor sequencing combined with other multiomics profiling.

Adaptive NK cells were enriched in responders and underwent profound transcriptomic changes during the therapy resulting in an active phenotype. LAG3+ Tregs expanded but based on the transcriptome profile became metabolically silent during the treatment. Lastly, higher baseline TCR clonality was observed in responding patients, and their expanding CD8+ T cell clones gained more cytotoxic and NK-like phenotype.

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