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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 5

Blocking the interactions of β1 and β2 integrins with their ligands does not affect T cell migration in the stroma of human lung tumors.

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Blocking the interactions of β1 and β2 integrins with their ligands does...
(A) Anti–β1 integrin and anti–β2 integrin Abs strongly inhibited adhesion of activated PBTs on VCAM-1 and ICAM-1. T cells pretreated or not with 10 μg/ml anti–β2 integrin mAb or anti–β1 integrin mAb were allowed to adhere on ICAM-1 or VCAM-1 layers for 10 minutes. After several washes, the number of remaining T cells was scored. Values are mean and SD from 3 different experiments. (B) Tracks of individual T cells treated (red) or not (green) with 10 μg/ml anti–β1 integrin and anti–β2 integrin mAbs in a human lung tumor slice during a 20-minute recording with a widefield microscope. (C) Motility coefficient of control and Ab-treated T cells within the tumor stroma. Values are mean and SD from experiments performed on tumor slices from 3 different lung cancer patients. At least 100 cells were analyzed per experiment. *P < 0.05; **P < 0.01. Scale bar: 100 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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