CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment.

Details

Serval ID
serval:BIB_7D2B6681B840
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment.
Journal
Cell
Author(s)
Di Pilato M., Kfuri-Rubens R., Pruessmann J.N., Ozga A.J., Messemaker M., Cadilha B.L., Sivakumar R., Cianciaruso C., Warner R.D., Marangoni F., Carrizosa E., Lesch S., Billingsley J., Perez-Ramos D., Zavala F., Rheinbay E., Luster A.D., Gerner M.Y., Kobold S., Pittet M.J., Mempel T.R.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
19/08/2021
Peer-reviewed
Oui
Volume
184
Number
17
Pages
4512-4530.e22
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Cytotoxic T lymphocyte (CTL) responses against tumors are maintained by stem-like memory cells that self-renew but also give rise to effector-like cells. The latter gradually lose their anti-tumor activity and acquire an epigenetically fixed, hypofunctional state, leading to tumor tolerance. Here, we show that the conversion of stem-like into effector-like CTLs involves a major chemotactic reprogramming that includes the upregulation of chemokine receptor CXCR6. This receptor positions effector-like CTLs in a discrete perivascular niche of the tumor stroma that is densely occupied by CCR7 <sup>+</sup> dendritic cells (DCs) expressing the CXCR6 ligand CXCL16. CCR7 <sup>+</sup> DCs also express and trans-present the survival cytokine interleukin-15 (IL-15). CXCR6 expression and IL-15 trans-presentation are critical for the survival and local expansion of effector-like CTLs in the tumor microenvironment to maximize their anti-tumor activity before progressing to irreversible dysfunction. These observations reveal a cellular and molecular checkpoint that determines the magnitude and outcome of anti-tumor immune responses.
Keywords
Animals, B7-H1 Antigen/metabolism, Cell Communication, Cell Movement, Cell Proliferation, Cell Survival, Chemokine CXCL16, Dendritic Cells/metabolism, Interleukin-12/metabolism, Interleukin-15/metabolism, Ligands, Lymph Nodes/metabolism, Melanoma/immunology, Melanoma/pathology, Mice, Inbred C57BL, Receptors, CXCR6/metabolism, T-Lymphocytes, Cytotoxic/immunology, Tumor Microenvironment, CCR7(+) dendritic cells, CTL, CXCL16, CXCR6, IL-15, TCF-1, TCGA, multiphoton intravital microscopy, scRNA-seq, tumor microenvironment
Pubmed
Web of science
Open Access
Yes
Create date
06/08/2021 9:53
Last modification date
21/01/2022 6:35
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