Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
Tumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumo...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/3b6f24f61d9f48d5acc98567f852e72c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | Tumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumoral injection of PcrV protein, a component of the Pseudomonas aeruginosa type 3 secretion system, suppressed tumor growth and increased apoptosis, inducible nitric oxide synthase (iNOS) expression, and the percentage of M1-polarized TAMs in tumor tissues. Furthermore, the intratumoral injection of PcrV-primed macrophages exerted a similar tumoricidal effect. In vitro analyses revealed that PcrV reeducated TAMs toward an antitumoral M1 phenotype and augmented their nitric oxide (NO)-mediated cytotoxicity against cancer cells. Mechanistically, we found that these effects were dependent on the activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated regulation of a PI3K/AKT/mTOR-glycolysis-NO feedback loop via direct interaction with TLR4. Collectively, these results revealed a potential role for PcrV in cancer immunotherapy through the targeting of TAM plasticity. |
|---|