Positive and negative influence of the matrix architecture on antitumor immune surveillance
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Cellular and Molecular Life Sciences
Review
Positive and negative influence of the matrix architecture on antitumor immune surveillance Elisa Peranzoni · Ana Rivas‑Caicedo · Houcine Bougherara · Hélène Salmon · Emmanuel Donnadieu
Received: 12 November 2012 / Revised: 18 March 2013 / Accepted: 8 April 2013 © Springer Basel 2013
Abstract The migration of T cells and access to tumor antigens is of utmost importance for the induction of protective anti-tumor immunity. Once having entered a malignant site, T cells encounter a complex environment composed of nontumor cells along with the extracellular matrix (ECM). It is now well accepted that a deregulated ECM favors tumor progression and metastasis. Recent progress in imaging technologies has also highlighted the impact of the matrix architecture found in solid tumor on immune cells and especially T cells. In this review, we argue that the ability of T cells to mount an antitumor response is dependent on the matrix structure, more precisely on the balance between pro-migratory reticular fiber networks and unfavorable migration zones composed of dense and aligned ECM structures. Thus, the matrix architecture, that has long been considered to merely provide the structural framework of connective tissues, can play a key role
E. Peranzoni · H. Bougherara · E. Donnadieu Inserm, U1016, Institut Cochin, Paris, France E. Peranzoni · H. Bougherara · E. Donnadieu Cnrs UMR8104, Paris, France
in facilitating or suppressing the antitumor immune surveillance. A new challenge in cancer therapy will be to develop approaches aimed at altering the architecture of the tumor stroma, rendering it more permissive to antitumor T cells. Keywords Tumor · T cells · Stroma · Extracellular matrix · Motility · Imaging Abbreviations 3D Three-dimensional ECM Extracellular matrix EMT Epithelial-mesenchymal transition FRC Fibroblastic reticular cells LOX Lysyl oxidase LTi Lymphoid tissue inducer MMP Metalloproteinases SHG Second-harmonic generation SLO Secondary lymphoid organs TACS Tumor-associated collagen signature TIL Tumor-infiltrating lymphocytes TLO Tertiary lymphoid organs
E. Peranzoni · H. Bougherara · E. Donnadieu Université Paris Descartes, Sorbonne Paris Cité, France
Introduction
A. Rivas‑Caicedo Alta Tecnología en Laboratorios SA de CV, Comoporis #45, El Caracol, Mexico, Mexico
A large majority of human solid tumors are of epithelial origin. However, carcinomas cannot be simply considered as a group of proliferating epithelial cells but rather as a complex ecosystem composed of a variety of cells organized in a specialized microenvironment, referred to as stroma. Indeed, the tumor stroma contains non-cancer cells, including endothelial cells and fibroblasts, along with the ECM. Although epithelial neoplastic cells and stromal cells are found in distinct areas (Fig. 1a), the growth of a tumor depends on dynamic and complex interactions between these cell populations.
H. Salmon Department of Oncological Sciences, Mount Sinai School of Medicine, 1425 Madison Av
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