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

Autor:	Alsaed B; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Smolander J; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Laitinen H; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Lin L; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Bobik N; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Lahtinen L; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Räsänen M; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Department of General Thoracic and Esophageal Surgery, Heart and Lung Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Jansouz S; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Translational Cancer Medicine Program (CAN-PRO), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Peltonen K; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Jokinen E; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Klievink J; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Ganesh K; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Translational Cancer Medicine Program (CAN-PRO), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki, Finland., Ainola M; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, and Department of Pulmonary Medicine, Heart and Lung Centre, Helsinki University Hospital, Helsinki, Finland., Sutinen E; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, and Department of Pulmonary Medicine, Heart and Lung Centre, Helsinki University Hospital, Helsinki, Finland., Rönty M; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Narvi E; Immuno-Oncology, Oncology Research, Orion Corporation, Turku, Finland., Thotakura A; Immuno-Oncology, Oncology Research, Orion Corporation, Turku, Finland., Saharinen P; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Translational Cancer Medicine Program (CAN-PRO), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki, Finland., Mustjoki S; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Ilonen I; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Department of General Thoracic and Esophageal Surgery, Heart and Lung Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Haikala HM; Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Nov; Vol. 10 (44), pp. eadq6830. Date of Electronic Publication: 2024 Oct 30.
DOI:	10.1126/sciadv.adq6830
Abstrakt:	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.
Databáze:	MEDLINE
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