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Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.
- Source :
-
Cell [Cell] 2019 Apr 04; Vol. 177 (2), pp. 414-427.e13. - Publication Year :
- 2019
-
Abstract
- PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal therapeutic use
Cell Line, Tumor
Exosomes metabolism
Humans
Immunotherapy
Lymphocyte Activation immunology
Male
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor antagonists & inhibitors
T-Lymphocytes immunology
Tumor Microenvironment physiology
B7-H1 Antigen metabolism
B7-H1 Antigen physiology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 177
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 30951669
- Full Text :
- https://doi.org/10.1016/j.cell.2019.02.016