Pentoxifylline changes the balance of immune cell population in breast tumor-infiltrating lymphocytes.
Breast cancer
Cytotoxic TILs
Pentoxifylline
Regulatory T cells
Tumor-infiltrating lymphocyte
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
06 May 2023
06 May 2023
Historique:
received:
12
03
2023
accepted:
17
04
2023
medline:
8
5
2023
pubmed:
7
5
2023
entrez:
6
5
2023
Statut:
epublish
Résumé
Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) is a promising approach for cancer treatment. Pentoxifylline (PTXF), a xanthine derivative, exhibits antitumor properties. This study aimed to investigate the impact of PTXF on the phenotype and function of TILs and splenocytes in a triple-negative breast cancer (TNBC) mouse model. TNBC was subcutaneously induced in BALB/c mice, followed by nine intraperitoneal injections of 100 mg/kg PTXF. TILs were then isolated by enzymatic digestion of tumors and cocultured with 4T1 cells. The proportion of regulatory T cells (Tregs) and cytotoxic T cells in TILs and splenocytes was assessed using flow cytometry. Transforming growth factor (TGF)-β and interferon (IFN)-γ production in TILs and splenocytes cultures was measured by ELISA. Relative expression of t-bet, foxp3, gata-3, and ror-γt in TILs and splenocytes was evaluated using real-time PCR. Tumor growth in PTXF-treated mice was significantly lower than that in the controls (P < 0.01). The frequency of regulatory and cytotoxic TILs in PTXF-treated mice was approximately half (P < 0.01) and twice (P < 0.05) that of the control group, respectively. The level of TGF-β and IFN-γ in the supernatant of PTXF-treated TILs was decreased and increased, respectively (P < 0.05). The relative expression of t-bet and foxp3 in the PTXF-treated mice compared to controls was increased and decreased, respectively (P < 0.05). Changes in the immune cell balance were less significant in the spleen compared to the TILs. PTXF treatment could limit the tumor growth and modify the regulatory-to-cytotoxic TILs ratio, as well as cytokine balance of TILs, in favor of antitumor responses.
Identifiants
pubmed: 37149505
doi: 10.1007/s12032-023-02034-5
pii: 10.1007/s12032-023-02034-5
pmc: PMC10164001
doi:
Substances chimiques
Pentoxifylline
SD6QCT3TSU
Antineoplastic Agents
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
168Subventions
Organisme : Iran University of Medical Sciences
ID : 33596
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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