In:
Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-25)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2021.736882
DOI:
10.3389/fonc.2021.736882.s001
DOI:
10.3389/fonc.2021.736882.s002
DOI:
10.3389/fonc.2021.736882.s003
DOI:
10.3389/fonc.2021.736882.s004
DOI:
10.3389/fonc.2021.736882.s005
DOI:
10.3389/fonc.2021.736882.s006
DOI:
10.3389/fonc.2021.736882.s007
DOI:
10.3389/fonc.2021.736882.s008
DOI:
10.3389/fonc.2021.736882.s009
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2649216-7
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