Regulation of the tumor immune microenvironment and vascular normalization in TNBC murine models by a novel peptide.
Immuno-activation
immunomodulating peptide
triple-negative breast cancer
tumor immune microenvironment
vascular normalization
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
14 05 2020
14 05 2020
Historique:
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
15
9
2020
Statut:
epublish
Résumé
Triple-negative breast cancer (TNBC) is a highly metastatic and aggressive disease with limited treatment options. Recently, the combination of the immune checkpoint inhibitor (ICI) atezolizumab (anti-PD-L1) with nab-paclitaxel was approved following a clinical trial that showed response rates in at least 43% of patients. While this approval marks a major advance in the treatment of TNBC it may be possible to improve the efficacy of ICI therapies through further modulation of the suppressive tumor immune microenvironment (TIME). Several factors may limit immune response in TNBC including aberrant growth factor signaling, such as VEGFR2 and cMet signaling, inefficient vascularization, poor delivery of drugs and immune cells, and the skewing of immune cell populations toward immunosuppressive phenotypes. Here we investigate the immune-modulating properties of AXT201, a novel 20 amino-acid integrin-binding peptide in two syngeneic mouse TNBC models: 4T1-BALB/c and NT4-FVB. AXT201 treatment improved survival in the NT4 model by 20% and inhibited the growth of 4T1 tumors by 47% over 22 days post-inoculation. Subsequent immunohistochemical analyses of 4T1 tumors also showed a 53% reduction in vascular density and a 184% increase in pericyte coverage following peptide treatment. Flow cytometry analyses demonstrated evidence of a more favorable anti-tumor immune microenvironment following treatment with AXT201, including significant decreases in the populations of T regulatory cells, monocytic myeloid-derived suppressor cells, and PD-L1 expressing cells and increased expression of T cell functional markers. Together, these findings demonstrate immune-activating properties of AXT201 that could be developed in combination with other immunomodulatory agents in the treatment of TNBC.
Identifiants
pubmed: 32923118
doi: 10.1080/2162402X.2020.1760685
pii: 1760685
pmc: PMC7458646
doi:
Substances chimiques
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
1760685Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007057
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA210482
Pays : United States
Organisme : NIH HHS
ID : S10 OD016374
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA138264
Pays : United States
Informations de copyright
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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