Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory
Broad Institute · University of California, San Francisco · +4 more institutions
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…
Citation impact
- FWCI
- 56.14
- Percentile
- 100%
- References
- 56
Authors
11- MPMauro Poggio
Broad Institute, University of California, San Francisco, California Institute for Regenerative Medicine, Broad Center
- THTianyi Hu
Broad Institute, University of California, San Francisco, California Institute for Regenerative Medicine, Broad Center
- CSChien-Chun Steven Pai
University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center
- BCBrandon Chu
Broad Institute, University of California, San Francisco, California Institute for Regenerative Medicine, Broad Center
- CDCassandra D. Belair
Broad Institute, University of California, San Francisco, California Institute for Regenerative Medicine, Broad Center
Topics & keywords
- Microvesicles
- Biology
- Cancer research
- PD-L1
- Antibody
- Secretion
- Exosome
- Effector
- Good health and well-being