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Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients
Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLI...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503454/ https://www.ncbi.nlm.nih.gov/pubmed/37720688 http://dx.doi.org/10.1080/2162402X.2023.2253644 |
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author | Adamo, Annalisa Frusteri, Cristina Pilotto, Sara Caligola, Simone Belluomini, Lorenzo Poffe, Ornella Giacobazzi, Luca Dusi, Silvia Musiu, Chiara Hu, Yushu Wang, Tian Rizzini, Davide Vella, Antonio Canè, Stefania Sartori, Giulia Insolda, Jessica Sposito, Marco Incani, Ursula Cesta Carbone, Carmine Piro, Geny Pettinella, Francesca Qi, Fang Wang, Dali Sartoris, Silvia De Sanctis, Francesco Scapini, Patrizia Dusi, Stefano Cassatella, Marco Antonio Bria, Emilio Milella, Michele Bronte, Vincenzo Ugel, Stefano |
author_facet | Adamo, Annalisa Frusteri, Cristina Pilotto, Sara Caligola, Simone Belluomini, Lorenzo Poffe, Ornella Giacobazzi, Luca Dusi, Silvia Musiu, Chiara Hu, Yushu Wang, Tian Rizzini, Davide Vella, Antonio Canè, Stefania Sartori, Giulia Insolda, Jessica Sposito, Marco Incani, Ursula Cesta Carbone, Carmine Piro, Geny Pettinella, Francesca Qi, Fang Wang, Dali Sartoris, Silvia De Sanctis, Francesco Scapini, Patrizia Dusi, Stefano Cassatella, Marco Antonio Bria, Emilio Milella, Michele Bronte, Vincenzo Ugel, Stefano |
author_sort | Adamo, Annalisa |
collection | PubMed |
description | Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients’ outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1β in only NP patients after ICI treatment. Moreover, using t-distributed stochastic neighbor embedding (t-SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression. |
format | Online Article Text |
id | pubmed-10503454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-105034542023-09-16 Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients Adamo, Annalisa Frusteri, Cristina Pilotto, Sara Caligola, Simone Belluomini, Lorenzo Poffe, Ornella Giacobazzi, Luca Dusi, Silvia Musiu, Chiara Hu, Yushu Wang, Tian Rizzini, Davide Vella, Antonio Canè, Stefania Sartori, Giulia Insolda, Jessica Sposito, Marco Incani, Ursula Cesta Carbone, Carmine Piro, Geny Pettinella, Francesca Qi, Fang Wang, Dali Sartoris, Silvia De Sanctis, Francesco Scapini, Patrizia Dusi, Stefano Cassatella, Marco Antonio Bria, Emilio Milella, Michele Bronte, Vincenzo Ugel, Stefano Oncoimmunology Original Research Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients’ outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1β in only NP patients after ICI treatment. Moreover, using t-distributed stochastic neighbor embedding (t-SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression. Taylor & Francis 2023-09-14 /pmc/articles/PMC10503454/ /pubmed/37720688 http://dx.doi.org/10.1080/2162402X.2023.2253644 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Original Research Adamo, Annalisa Frusteri, Cristina Pilotto, Sara Caligola, Simone Belluomini, Lorenzo Poffe, Ornella Giacobazzi, Luca Dusi, Silvia Musiu, Chiara Hu, Yushu Wang, Tian Rizzini, Davide Vella, Antonio Canè, Stefania Sartori, Giulia Insolda, Jessica Sposito, Marco Incani, Ursula Cesta Carbone, Carmine Piro, Geny Pettinella, Francesca Qi, Fang Wang, Dali Sartoris, Silvia De Sanctis, Francesco Scapini, Patrizia Dusi, Stefano Cassatella, Marco Antonio Bria, Emilio Milella, Michele Bronte, Vincenzo Ugel, Stefano Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title | Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title_full | Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title_fullStr | Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title_full_unstemmed | Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title_short | Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
title_sort | immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular flip-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503454/ https://www.ncbi.nlm.nih.gov/pubmed/37720688 http://dx.doi.org/10.1080/2162402X.2023.2253644 |
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