CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment
In: Cell, Jg. 184 (2021-08-01), Heft 17
academicJournal
- 4512 - 4530.e22
Zugriff:
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+ dendritic cells (DCs) expressing the CXCR6 ligand CXCL16. CCR7+ 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.
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CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment
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Autor/in / Beteiligte Person: | Di Pilato, Mauro ; Kfuri-Rubens, Raphael ; Pruessmann, Jasper N ; Ozga, Aleksandra J ; Messemaker, Marius ; Cadilha, Bruno L ; Sivakumar, Ramya ; Cianciaruso, Chiara ; Warner, Ross D ; Marangoni, Francesco ; Carrizosa, Esteban ; Lesch, Stefanie ; Billingsley, James ; Perez-Ramos, Daniel ; Zavala, Fidel ; Rheinbay, Esther ; Luster, Andrew D ; Gerner, Michael Y ; Kobold, Sebastian ; Pittet, Mikael J ; Mempel, Thorsten R |
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Zeitschrift: | Cell, Jg. 184 (2021-08-01), Heft 17 |
Veröffentlichung: | eScholarship, University of California, 2021 |
Medientyp: | academicJournal |
Umfang: | 4512 - 4530.e22 |
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