Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma.
Biological sciences
Cancer
Immunology
Microenvironment
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
16 Sep 2022
16 Sep 2022
Historique:
received:
07
12
2021
revised:
20
05
2022
accepted:
18
08
2022
entrez:
13
9
2022
pubmed:
14
9
2022
medline:
14
9
2022
Statut:
epublish
Résumé
The outcome for children with high-risk neuroblastoma is poor despite intensive multi-modal treatment protocols. Toxicity from current treatments is significant, and novel approaches are needed to improve outcome. Cyclophosphamide (CPM) is a key component of current chemotherapy regimens and is known to have immunomodulatory effects. However, this has not been investigated in the context of tumor infiltrating lymphocytes in neuroblastoma. Using murine models of neuroblastoma, the immunomodulatory effects of low-dose CPM were investigated using detailed immunophenotyping. We demonstrated that CPM resulted in a specific depletion of intratumoral T regulatory cells by apoptosis, and when combined with anti-PD-1 antibody therapy, this resulted in improved therapeutic efficacy. CPM combined with anti-PD-1 therapy was demonstrated to be an effective combinational therapy, with metronomic CPM found to be more effective than single dosing in more resistant tumor models. Overall, this pre-clinical data strongly support clinical evaluation of such combination strategies in neuroblastoma.
Identifiants
pubmed: 36097618
doi: 10.1016/j.isci.2022.104995
pii: S2589-0042(22)01267-6
pmc: PMC9463572
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104995Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
S.A.B. has acted as a consultant for a number of biotech companies and has received institutional support for grants and patents from BioInvent International. JCG has acted as a consultant on advisory boards for a number of pharmaceutical companies and has received institutional grant support from Bristol Myers Squibb (BMS) and EUSA, as Celgene was acquired by BMS.
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