Research Paper Volume 15, Issue 6 pp 1791—1807
PD-L1ATTAC mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy
- 1 Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain
- 2 Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain
- 3 Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Division of Genome Biology, Karolinska Institute, S-171 21 Stockholm, Sweden
Received: January 14, 2023 Accepted: February 27, 2023 Published: March 22, 2023
https://doi.org/10.18632/aging.204598How to Cite
Copyright: © 2023 Fueyo-Marcos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Antibodies targeting the PD-1 receptor and its ligand PD-L1 have shown impressive responses in some tumors of bad prognosis. We hypothesized that, since immunosuppressive cells might present several immune checkpoints on their surface, the selective elimination of PD-L1 expressing cells could be efficacious in enabling the activation of antitumoral immune responses. To address this question, we developed an inducible suicidal knock-in mouse allele of Pd-l1 (PD-L1ATTAC) which allows for the tracking and specific elimination of PD-L1-expressing cells in adult tissues. Consistent with our hypothesis, elimination of PD-L1 expressing cells from the mouse peritoneum increased the septic response to lipopolysaccharide (LPS), due to an exacerbated inflammatory response to the endotoxin. In addition, mice depleted of PD-L1+ cells were resistant to colon cancer peritoneal allografts, which was associated with a loss of immunosuppressive B cells and macrophages, concomitant with an increase in activated cytotoxic CD8 T cells. Collectively, these results illustrate the usefulness of PD-L1ATTAC mice for research in immunotherapy and provide genetic support to the concept of targeting PD-L1 expressing cells in cancer.