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Pentoxifylline Changes the Balance of Immune Cell Population in Breast Tumor-Infiltrating Lymphocytes Publisher Pubmed



Kazemi MH1, 2, 5 ; Shokrollahi Barough M1, 2 ; Momenivarposhti Z3 ; Ghanavatinejad A4 ; Zarehzadeh Mehrabadi A1, 5 ; Sadeghi B2, 6 ; Falak R1, 5
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. BOX: 15179/64311, Tehran, Iran
  3. 3. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
  5. 5. Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Translational Cell Therapy Research (TCR), Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden

Source: Medical Oncology Published:2023


Abstract

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. © 2023, The Author(s).
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1. Decrease of Tumor-Infiltrating Regulatory T Cells Using Pentoxifylline: An Ex Vivo Analysis in Triple-Negative Breast Cancer Mouse Model, Iranian Journal of Allergy# Asthma and Immunology (2022)