Tumor extracellular matrix stiffness promptly modulates the phenotype and gene expression of infiltrating t lymphocytes

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number5862
JournalInternational Journal of Molecular Sciences
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 1 2021

Keywords

  • 3D culture
  • Extracellular matrix
  • T lymphocytes
  • Tumor microenvironment

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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