Journal
CELL
Volume 184, Issue 17, Pages 4512-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.07.015
Keywords
-
Categories
Funding
- Harvard Medical School Foundry award
- National Institutes of Health (NIH) [P01-CA240239, R01 AI084880, R01 CA218579, R01 AI123349, R01 CA206890, R01 CA204028, R01 AI134713, R21AI142667]
- BMBF project Oncoattract
- MSC network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union [955575]
- Bavarian Ministry for Economic Affairs (CARMOUFLAGE)
- ERC grant [756017]
- i-Target: Immunotargeting of Cancer - Elite Network of Bavaria
- Melanoma Research Alliance Established Investigator Award [827872]
- Melanoma Research Foundation
- ISREC Foundation
- EMBO fellowship [ALTF534-2015]
- Marie Curie Global Fellowship [750973]
- DFG [PR 1652/1-1, PR 1652/2-1]
- German Academic Scholarship Foundation
- LMU Prosa Scholarship
- Swiss National Science Foundation Early Postdoctoral Mobility Award [P3BEP3_165406]
- American Association for Cancer Research Basic Science Fellowship Program [18-4001-OZGA]
- Bloomberg Philanthropies
- Marie Curie Actions (MSCA) [955575, 750973] Funding Source: Marie Curie Actions (MSCA)
Ask authors/readers for more resources
The conversion of stem-like CTLs into effector-like CTLs involves chemotactic reprogramming with upregulation of chemokine receptor CXCR6. CXCR6 expression and IL-15 trans-presentation are crucial for the survival and local expansion of effector-like CTLs in the tumor microenvironment.
Cytotoxic T lymphocyte (CTL) responses against tumors are maintained by stem-like memory cells that selfrenew 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available