Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes
The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochem...
| Main Authors: | , , , , , , , , , , , , , , , , |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Maila Chirivì Fabio Maiullari Marika Milan Dario Presutti Chiara Cordiglieri Mariacristina Crosti Maria Lucia Sarnicola Andrea Soluri Marina Volpi Wojciech Święszkowski Daniele Prati Marta Rizzi Marco Costantini Dror Seliktar Chiara Parisi Claudia Bearzi Roberto Rizzi |
| author_facet | Maila Chirivì Fabio Maiullari Marika Milan Dario Presutti Chiara Cordiglieri Mariacristina Crosti Maria Lucia Sarnicola Andrea Soluri Marina Volpi Wojciech Święszkowski Daniele Prati Marta Rizzi Marco Costantini Dror Seliktar Chiara Parisi Claudia Bearzi Roberto Rizzi |
| author_sort | Maila Chirivì |
| collection | DOAJ |
| description | The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4<sup>+</sup> and CD8<sup>+</sup> lymphocytes, and innate immunity cells. These populations interface with each other to prepare a conservative response, capable of evading the defense mechanisms implemented by the host’s immune system. The presence or absence, in particular, of cytotoxic CD8<sup>+</sup> cells in the vicinity of the main tumor mass, is able to predict, respectively, the success or failure of drug therapy. Among various mechanisms of immunescaping, in this study, we characterized the modulation of the phenotypic profile of CD4<sup>+</sup> and CD8<sup>+</sup> cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional <i>in vitro</i> system, able to recapitulate the rheological and stiffness properties of the tumor ECM. |
| first_indexed | 2024-03-10T10:52:53Z |
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| language | English |
| last_indexed | 2024-03-10T10:52:53Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-add9a0e00c28425c98b902b004f54a612023-11-21T22:04:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211586210.3390/ijms22115862Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T LymphocytesMaila Chirivì0Fabio Maiullari1Marika Milan2Dario Presutti3Chiara Cordiglieri4Mariacristina Crosti5Maria Lucia Sarnicola6Andrea Soluri7Marina Volpi8Wojciech Święszkowski9Daniele Prati10Marta Rizzi11Marco Costantini12Dror Seliktar13Chiara Parisi14Claudia Bearzi15Roberto Rizzi16Fondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyInstitute of Physical Chemistry Polish Academy of Sciences, Marcina Kasprzaka 44/52, 01-224 Warszawa, PolandFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyInstitute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, ItalyFaculty of Materials Science and Engineering, Warsaw University of Technology, 02-507 Warsaw, PolandFaculty of Materials Science and Engineering, Warsaw University of Technology, 02-507 Warsaw, PolandDepartment of Transfusion Medicine and Hematology, IRCCS Granda Hospital Maggiore Policlinico Foundation, Via Francesco Sforza 35, 20122 Milan, ItalyUfficio Programmazione e Grant Office, National Research Council of Italy (UPGO-CNR), Piazzale Aldo Moro 7, 00185 Rome, ItalyInstitute of Physical Chemistry Polish Academy of Sciences, Marcina Kasprzaka 44/52, 01-224 Warszawa, PolandDepartment of Biomedical Engineering, Technion Institute, Haifa 32000, IsraelInstitute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyFondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, ItalyThe immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4<sup>+</sup> and CD8<sup>+</sup> lymphocytes, and innate immunity cells. These populations interface with each other to prepare a conservative response, capable of evading the defense mechanisms implemented by the host’s immune system. The presence or absence, in particular, of cytotoxic CD8<sup>+</sup> cells in the vicinity of the main tumor mass, is able to predict, respectively, the success or failure of drug therapy. Among various mechanisms of immunescaping, in this study, we characterized the modulation of the phenotypic profile of CD4<sup>+</sup> and CD8<sup>+</sup> cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional <i>in vitro</i> system, able to recapitulate the rheological and stiffness properties of the tumor ECM.https://www.mdpi.com/1422-0067/22/11/5862tumor microenvironmentextracellular matrixT lymphocytes3D culture |
| spellingShingle | Maila Chirivì Fabio Maiullari Marika Milan Dario Presutti Chiara Cordiglieri Mariacristina Crosti Maria Lucia Sarnicola Andrea Soluri Marina Volpi Wojciech Święszkowski Daniele Prati Marta Rizzi Marco Costantini Dror Seliktar Chiara Parisi Claudia Bearzi Roberto Rizzi Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes International Journal of Molecular Sciences tumor microenvironment extracellular matrix T lymphocytes 3D culture |
| title | Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes |
| title_full | Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes |
| title_fullStr | Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes |
| title_full_unstemmed | Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes |
| title_short | Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes |
| title_sort | tumor extracellular matrix stiffness promptly modulates the phenotype and gene expression of infiltrating t lymphocytes |
| topic | tumor microenvironment extracellular matrix T lymphocytes 3D culture |
| url | https://www.mdpi.com/1422-0067/22/11/5862 |
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