Galectin-3 captures interferon-gamma in the tumor matrix reducing chemokine gradient production and T-cell tumor infiltration

Monica Gordon-Alonso (), Thibault Hirsch, Claude Wildmann and Pierre van der Bruggen ()
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Monica Gordon-Alonso: Université catholique de Louvain
Thibault Hirsch: Université catholique de Louvain
Claude Wildmann: Université catholique de Louvain
Pierre van der Bruggen: Université catholique de Louvain

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract The presence of T cells in tumors predicts overall survival for cancer patients. However, why most tumors are poorly infiltrated by T cells is barely understood. T-cell recruitment towards the tumor requires a chemokine gradient of the critical IFNγ-induced chemokines CXCL9/10/11. Here, we describe how tumors can abolish IFNγ-induced chemokines, thereby reducing T-cell attraction. This mechanism requires extracellular galectin-3, a lectin secreted by tumors. Galectins bind the glycans of glycoproteins and form lattices by oligomerization. We demonstrate that galectin-3 binds the glycans of the extracellular matrix and those decorating IFNγ. In mice bearing human tumors, galectin-3 reduces IFNγ diffusion through the tumor matrix. Galectin antagonists increase intratumoral IFNγ diffusion, CXCL9 gradient and tumor recruitment of adoptively transferred human CD8+ T cells specific for a tumor antigen. Transfer of T cells reduces tumor growth only if galectin antagonists are injected. Considering that most human cytokines are glycosylated, galectin secretion could be a general strategy for tumor immune evasion.

Date: 2017
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DOI: 10.1038/s41467-017-00925-6

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