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Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma

Immunotherapy with anti‐PD1/PD‐L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti‐PD1/PD‐L1 and dendritic cell (DC) therapy to optimally induce effective anti‐tumor immunity in MPM in both humans and mice. D...

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Autores principales: van Gulijk, Mandy, Belderbos, Bob, Dumoulin, Daphne, Cornelissen, Robin, Bezemer, Koen, Klaase, Larissa, Dammeijer, Floris, Aerts, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092125/
https://www.ncbi.nlm.nih.gov/pubmed/36104949
http://dx.doi.org/10.1002/ijc.34293
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author van Gulijk, Mandy
Belderbos, Bob
Dumoulin, Daphne
Cornelissen, Robin
Bezemer, Koen
Klaase, Larissa
Dammeijer, Floris
Aerts, Joachim
author_facet van Gulijk, Mandy
Belderbos, Bob
Dumoulin, Daphne
Cornelissen, Robin
Bezemer, Koen
Klaase, Larissa
Dammeijer, Floris
Aerts, Joachim
author_sort van Gulijk, Mandy
collection PubMed
description Immunotherapy with anti‐PD1/PD‐L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti‐PD1/PD‐L1 and dendritic cell (DC) therapy to optimally induce effective anti‐tumor immunity in MPM in both humans and mice. Data of nine MPM patients treated with DC therapy and sequential anti‐PD1 treatment were collected and analyzed for progression‐free survival (PFS) and overall survival (OS). Survival and T‐cell responses were monitored in AC29 mesothelioma‐bearing mice treated concurrently with the combination therapy; additionally, the role of the tumor‐draining lymph node (TDLN) was investigated. The combination therapy resulted in a median OS and PFS of 17.7 and 8.0 months, respectively. Grade 3 to 4 treatment‐related adverse events had not been reported. Survival of the mesothelioma‐bearing mice treated with the combination therapy was longer than that of untreated mice, and coincided with improved T‐cell activation in peripheral blood and less T‐cell exhaustion in end stage tumors. Comparable results were obtained when solely the TDLN was targeted. We concluded that this combination therapy is safe and shows promising OS and PFS. The murine data support that PD‐L1 treatment may reinvigorate the T‐cell responses induced by DC therapy, which may primarily be the result of TDLN targeting.
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spelling pubmed-100921252023-04-13 Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma van Gulijk, Mandy Belderbos, Bob Dumoulin, Daphne Cornelissen, Robin Bezemer, Koen Klaase, Larissa Dammeijer, Floris Aerts, Joachim Int J Cancer CANCER THERAPY AND PREVENTION Immunotherapy with anti‐PD1/PD‐L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti‐PD1/PD‐L1 and dendritic cell (DC) therapy to optimally induce effective anti‐tumor immunity in MPM in both humans and mice. Data of nine MPM patients treated with DC therapy and sequential anti‐PD1 treatment were collected and analyzed for progression‐free survival (PFS) and overall survival (OS). Survival and T‐cell responses were monitored in AC29 mesothelioma‐bearing mice treated concurrently with the combination therapy; additionally, the role of the tumor‐draining lymph node (TDLN) was investigated. The combination therapy resulted in a median OS and PFS of 17.7 and 8.0 months, respectively. Grade 3 to 4 treatment‐related adverse events had not been reported. Survival of the mesothelioma‐bearing mice treated with the combination therapy was longer than that of untreated mice, and coincided with improved T‐cell activation in peripheral blood and less T‐cell exhaustion in end stage tumors. Comparable results were obtained when solely the TDLN was targeted. We concluded that this combination therapy is safe and shows promising OS and PFS. The murine data support that PD‐L1 treatment may reinvigorate the T‐cell responses induced by DC therapy, which may primarily be the result of TDLN targeting. John Wiley & Sons, Inc. 2022-10-03 2023-04-01 /pmc/articles/PMC10092125/ /pubmed/36104949 http://dx.doi.org/10.1002/ijc.34293 Text en © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle CANCER THERAPY AND PREVENTION
van Gulijk, Mandy
Belderbos, Bob
Dumoulin, Daphne
Cornelissen, Robin
Bezemer, Koen
Klaase, Larissa
Dammeijer, Floris
Aerts, Joachim
Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title_full Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title_fullStr Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title_full_unstemmed Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title_short Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
title_sort combination of pd‐1/pd‐l1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma
topic CANCER THERAPY AND PREVENTION
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092125/
https://www.ncbi.nlm.nih.gov/pubmed/36104949
http://dx.doi.org/10.1002/ijc.34293
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