Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes

International Journal of Molecular Sciences

Dror Seliktar¹  Daniele Prati²  Wojciech Święszkowski³  Marina Volpi³  Fabio Maiullari⁴  MariaLucia Sarnicola⁴  Mariacristina Crosti⁴  Maila Chirivì⁴  Roberto Rizzi⁴  Chiara Cordiglieri⁴  Claudia Bearzi⁴  Marika Milan⁴  Chiara Parisi⁵  Andrea Soluri⁵  Marco Costantini⁶  Dario Presutti⁶  Marta Rizzi⁷ 

[1] Department of Biomedical Engineering, Technion Institute, Haifa 32000, Israel;Department of Transfusion Medicine and Hematology, IRCCS Ca ‘Granda Hospital Maggiore Policlinico Foundation, Via Francesco Sforza 35, 20122 Milan, Italy;Faculty of Materials Science and Engineering, Warsaw University of Technology, 02-507 Warsaw, Poland;Fondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy;Institute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Via Ercole Ramarini, 32, Monterotondo, 00015 Rome, Italy;Institute of Physical Chemistry Polish Academy of Sciences, Marcina Kasprzaka 44/52, 01-224 Warszawa, Poland;Ufficio Programmazione e Grant Office, National Research Council of Italy (UPGO-CNR), Piazzale Aldo Moro 7, 00185 Rome, Italy;

关键词: tumor microenvironment;    extracellular matrix;    T lymphocytes;    3D culture;   

DOI  :  10.3390/ijms22115862

来源: DOAJ

【 摘 要 】

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⁺ and CD8⁺ 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⁺ 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⁺ and CD8⁺ cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional in vitro system, able to recapitulate the rheological and stiffness properties of the tumor ECM.

【 授权许可】

Unknown