Ex vivo modeling of precision immuno-oncology responses in lung cancer

Bassel Alsaed, Johannes Smolander, Hanna Laitinen, Linh Lin, Nina Bobik, Lilja Lahtinen, Mikko Räsänen, Shadi Jansouz, Karita Peltonen, Emmi Jokinen, Jay Klievink, Keerthana Ganesh, Mari Ainola, Eva Sutinen, Mikko Rönty, Elli Narvi, Anil Thotakura, Pipsa Saharinen, Satu Mustjoki, Ilkka IlonenHeidi M. Haikala

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Despite immunotherapy's promise in cancer treatment, patient responses vary substantially because of the individual nature of the immune system and the lack of reliable biomarkers. To address this issue, we developed a precision ex vivo platform that integrates patient-specific tumor and immune cells to study the mechanisms of antitumor immune response, predict immunotherapy outcomes, and identify effective treatments. This platform revealed unique single-cell immune response mechanisms and sensitivities to standard-of-care immunotherapies. Furthermore, we were able to identify a synergistic combination of anti-programmed cell death protein 1 (anti-PD-1) together with a Casitas B lineage lymphoma-b inhibitor that overcame anti-PD-1 resistance in selected patient samples. Activation of the interferon-γ-stimulated cytokines predicted combination efficacy, while immunosuppressive cytokines were associated with poor response. Our findings underscore the platform's potential in tailoring immunotherapies and advancing drug development, offering avenues for personalized cancer treatment.

Originalspråkengelska
Artikelnummereadq6830
TidskriftScience Advances
Volym10
Nummer44
Antal sidor15
ISSN2375-2548
DOI
StatusPublicerad - 30 okt. 2024
MoE-publikationstypA1 Tidskriftsartikel-refererad

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  • 3122 Cancersjukdomar

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