Unknown

Dataset Information

0

Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy.


ABSTRACT: 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.

SUBMITTER: Rivera LB 

PROVIDER: S-EPMC4438771 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy.

Rivera Lee B LB   Meyronet David D   Hervieu Valérie V   Frederick Mitchell J MJ   Bergsland Emily E   Bergers Gabriele G  

Cell reports 20150416 4


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, r  ...[more]

Similar Datasets

| 2724171 | ecrin-mdr-crc
| S-EPMC4686232 | biostudies-literature
| S-EPMC8559549 | biostudies-literature
| S-EPMC3057433 | biostudies-literature
2016-07-15 | GSE80436 | GEO
| S-EPMC5673093 | biostudies-literature
| S-EPMC5256137 | biostudies-literature
| S-EPMC7236890 | biostudies-literature
| S-EPMC6675057 | biostudies-literature
| S-EPMC5104278 | biostudies-literature