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Published on: February 8, 2018
Decrease of Tumor-infiltrating Regulatory T Cells Using Pentoxifylline: An Ex Vivo Analysis in Triple-negative Breast
Mohammad Hossein Kazemi1, Mahdieh Shokrollahi Barough2, Alireza Ghanavatinejad3
1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Department of ATMP, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. Kazemi.m03@iums.ac.ir.
Pentoxifylline (PTXF) effectively reduces regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs) from triple-negative breast cancer (TNBC) models without impacting cell viability. This suggests PTXF can enhance TIL therapy by modulating immune responses.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and characterized by high tumor-infiltrating lymphocytes (TILs).
- TIL therapy shows promise for TNBC, but regulatory T cells (Tregs) within TILs can suppress anti-tumor immunity.
- Pentoxifylline (PTXF), a xanthine derivative, may modulate immune cell populations, including Tregs.
Purpose of the Study:
- To investigate the ex vivo effects of pentoxifylline (PTXF) on the proportion of regulatory T cells (Tregs) within tumor-infiltrating lymphocytes (TILs) from a mouse model of triple-negative breast cancer (TNBC).
- To assess the impact of PTXF on TIL viability and cytokine production in the context of IL-2-mediated expansion.
Main Methods:
- TNBC was induced in BALB/c mice using 4T1 cells.
- TILs were isolated and cultured with or without 4T1 cells, IL-2, and varying concentrations of PTXF for 24-72 hours.
- Cell viability (MTT assay), Treg proportion (flow cytometry), and cytokine levels (ELISA) were analyzed.
Main Results:
- Pentoxifylline (PTXF) demonstrated no significant toxicity to TILs at tested concentrations.
- PTXF significantly decreased the proportion of Tregs in a dose-dependent manner.
- PTXF altered cytokine profiles, increasing interferon-gamma and decreasing tumor growth factor-beta.
Conclusions:
- Ex vivo treatment with pentoxifylline can reduce Treg populations during IL-2-mediated TIL expansion for TNBC.
- PTXF treatment shifts the cytokine balance in TILs towards an anti-tumor immune response.
- Pentoxifylline represents a potential adjuvant therapy to enhance TIL-based immunotherapy for TNBC.
