| Title: |
Intratumoral Myeloid Cells Regulate Responsiveness and Resistance to Antiangiogenic Therapy |
| Authors: |
Lee B. Rivera, David Meyronet, Valérie Hervieu, Mitchell J. Frederick, Emily Bergsland, Gabriele Bergers |
| Source: |
Cell Reports, Vol 11, Iss 4, Pp 577-591 (2015) |
| Publisher Information: |
Elsevier, 2015. |
| Publication Year: |
2015 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
Antiangiogenic therapy is commonly used in the clinic, but its beneficial effects are short-lived, leading to tumor relapse within months. Here, we found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in mouse models of pancreatic neuroendocrine and mammary tumors. In response, tumors reinitiated angiogenesis and immune suppression by activating PI3K signaling in all CD11b+ cells, rendering tumors nonresponsive to VEGF/VEGFR inhibition. Adaptive resistance was also associated with an increase in Gr1+CD11b+ cells, but targeting Gr1+ cells was not sufficient to further sensitize angiogenic blockade because tumor-associated macrophages (TAMs) would compensate for the lack of such cells and vice versa, leading to an oscillating pattern of distinct immune-cell populations. However, PI3K inhibition in CD11b+ myeloid cells generated an enduring angiostatic and immune-stimulatory environment in which antiangiogenic therapy remained efficient. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124715003460; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2015.03.055 |
| Access URL: |
https://doaj.org/article/ee25e725c48742758930c38e4a3e7556 |
| Accession Number: |
edsdoj.25e725c48742758930c38e4a3e7556 |
| Database: |
Directory of Open Access Journals |
