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Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors
Hélène Salmon, … , Fathia Mami-Chouaib, Emmanuel Donnadieu
Hélène Salmon, … , Fathia Mami-Chouaib, Emmanuel Donnadieu
Published February 1, 2012
Citation Information: J Clin Invest. 2012;122(3):899-910. https://doi.org/10.1172/JCI45817.
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Research Article Immunology Article has an altmetric score of 24

Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

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Abstract

Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown. By combining immunostaining and real-time imaging in viable slices of human lung tumors, we revealed that the density and the orientation of the stromal extracellular matrix likely play key roles in controlling the migration of T cells. Active T cell motility, dependent on chemokines but not on β1 or β2 integrins, was observed in loose fibronectin and collagen regions, whereas T cells migrated poorly in dense matrix areas. Aligned fibers in perivascular regions and around tumor epithelial cell regions dictated the migratory trajectory of T cells and restricted them from entering tumor islets. Consistently, matrix reduction with collagenase increased the ability of T cells to contact cancer cells. Thus, the stromal extracellular matrix influences antitumor immunity by controlling the positioning and migration of T cells. Understanding the mechanisms by which this collagen network is generated has the potential to aid in the development of new therapeutics.

Authors

Hélène Salmon, Katarzyna Franciszkiewicz, Diane Damotte, Marie-Caroline Dieu-Nosjean, Pierre Validire, Alain Trautmann, Fathia Mami-Chouaib, Emmanuel Donnadieu

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Figure 7

Matrix fibers surrounding tumor islets restrict T cells from contacting tumor cells.

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Matrix fibers surrounding tumor islets restrict T cells from contacting ...
(A) Representative image of a human lung tumor slice stained for fibronectin (red), EpCAM (blue), and CD3 (green), demonstrating the presence of parallel fibers adjacent to the tumor cell regions. (B) Representative SEM image showing ECM strands parallel to the tumor cell regions. (C) Motility pattern of T cells (Hoechst; green) introduced into a human lung tumor slice stained for fibronectin (red) and EpCAM (blue). Also shown are tracks (middle) and trajectory vectors (right) during a 20-minute recording. (D) Angle between tumor-stroma boundary and trajectory vector of individual T cells, measured in tumor slices from 4 different lung cancer patients. Dashed line denotes 45°, the expected result from a cell population migrating with no directional bias. (E) Migration pattern of T cells in stromal regions adjacent to the tumor-stroma interface. Graphs represent the proportion of tracks whose end positions after the 20-minute recording were within each 90° segment (left scheme). The starting position of each cell was set at the x-y axis intersection, with the x axis parallel to the tumor-stroma boundary. Dashed lines denote 22.5°, the expected result from a cell population migrating with no directional bias. (F) Gap size between fibronectin fibers in 50-μm increments from the tumor islets. Values in E and F are mean and SD from experiments performed on tumor slices from 4 different lung cancer patients. ***P < 0.001. Scale bar: 50 μm (A); 10 μm (B); 100 μm (C).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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