Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer
The tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metast...
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| Format: | Article |
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/101885 |
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| author | Joseph Ackermann Chiara Bernard Philemon Sirven Helene Salmon Massimiliano Fraldi Martine D Ben Amar |
| author_facet | Joseph Ackermann Chiara Bernard Philemon Sirven Helene Salmon Massimiliano Fraldi Martine D Ben Amar |
| author_sort | Joseph Ackermann |
| collection | DOAJ |
| description | The tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metastasis depend. These include exclusion of immune cells from the tumor nest, cancer progression, and inhibition of T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data into a minimal dynamical system, explore the variety of outcomes, and finally establish a spatio-temporal model that explains the cell distribution. We reproduce that cancer-associated fibroblasts act as a barrier to tumor expansion, but also reduce the efficiency of the immune response. Our conclusion is that the final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxicity, and fibroblast activity. However, despite the existence of a wide range of scenarios, distinct trajectories, and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols. |
| format | Article |
| id | doaj-art-a22bc9abb4b64dd0bdf0d1a6d0245810 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-a22bc9abb4b64dd0bdf0d1a6d02458102025-08-20T02:16:33ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.101885Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancerJoseph Ackermann0https://orcid.org/0000-0001-9218-6655Chiara Bernard1Philemon Sirven2Helene Salmon3Massimiliano Fraldi4Martine D Ben Amar5https://orcid.org/0000-0001-9132-2053Laboratoire Jean Perrin, Sorbonne Université, Paris, France; Laboratoire de Physique de l’Ecole normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, Paris, FranceDepartment of Structures for Engineering and Architecture, University of Naples "Federico II", Naples, ItalyInstitut Curie, PSL Research University, INSERM, Paris, FranceInstitut Curie, PSL Research University, INSERM, Paris, FranceLaboratoire de Physique de l’Ecole normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, Paris, France; Department of Structures for Engineering and Architecture, University of Naples "Federico II", Naples, ItalyLaboratoire de Physique de l’Ecole normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, Paris, France; Institut Universitaire de Cancérologie, Faculté de médecine, Sorbonne Université, Paris, FranceThe tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metastasis depend. These include exclusion of immune cells from the tumor nest, cancer progression, and inhibition of T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data into a minimal dynamical system, explore the variety of outcomes, and finally establish a spatio-temporal model that explains the cell distribution. We reproduce that cancer-associated fibroblasts act as a barrier to tumor expansion, but also reduce the efficiency of the immune response. Our conclusion is that the final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxicity, and fibroblast activity. However, despite the existence of a wide range of scenarios, distinct trajectories, and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols.https://elifesciences.org/articles/101885tumor microenvironmentimmune responselung cancerdynamical systemmixture modelOnsager's variational principle |
| spellingShingle | Joseph Ackermann Chiara Bernard Philemon Sirven Helene Salmon Massimiliano Fraldi Martine D Ben Amar Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer eLife tumor microenvironment immune response lung cancer dynamical system mixture model Onsager's variational principle |
| title | Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer |
| title_full | Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer |
| title_fullStr | Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer |
| title_full_unstemmed | Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer |
| title_short | Mechanistic insight for T-cell exclusion by cancer-associated fibroblasts in human lung cancer |
| title_sort | mechanistic insight for t cell exclusion by cancer associated fibroblasts in human lung cancer |
| topic | tumor microenvironment immune response lung cancer dynamical system mixture model Onsager's variational principle |
| url | https://elifesciences.org/articles/101885 |
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