Author:
Peranzoni Elisa,Lemoine Jean,Vimeux Lene,Feuillet Vincent,Barrin Sarah,Kantari-Mimoun Chahrazade,Bercovici Nadège,Guérin Marion,Biton Jérôme,Ouakrim Hanane,Régnier Fabienne,Lupo Audrey,Alifano Marco,Damotte Diane,Donnadieu Emmanuel
Abstract
In a large proportion of cancer patients, CD8 T cells are excluded from the vicinity of cancer cells. The inability of CD8 T cells to reach tumor cells is considered an important mechanism of resistance to cancer immunotherapy. We show that, in human lung squamous-cell carcinomas, exclusion of CD8 T cells from tumor islets is correlated with a poor clinical outcome and with a low lymphocyte motility, as assessed by dynamic imaging on fresh tumor slices. In the tumor stroma, macrophages mediate lymphocyte trapping by forming long-lasting interactions with CD8 T cells. Using a mouse tumor model with well-defined stromal and tumor cell areas, macrophages were depleted with PLX3397, an inhibitor of colony-stimulating factor-1 receptor (CSF-1R). Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets. Although this treatment alone has minor effects on tumor growth, its combination with anti–PD-1 therapy further increases the accumulation of CD8 T cells in close contact with malignant cells and delays tumor progression. These data suggest that the reduction of macrophage-mediated T cell exclusion increases tumor surveillance by CD8 T cells and renders tumors more responsive to anti–PD-1 treatment.
Funder
Ligue Contre le Cancer
Plan cancer France
SIRIC France
Fondation de France
Associazione Italiana per la Ricerca sul Cancro
Publisher
Proceedings of the National Academy of Sciences
Cited by
539 articles.
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