Open AccessDecrease of Tumor-infiltrating Regulatory T Cells using Pentoxifylline: An Ex Vivo Analysis in Triple-negative Breast Cancer Mouse Model
Author(s) -
Mohammad Kazemi,
Mahdieh Shokrollahi Barough,
Alireza Ghanavatinejad,
Zahra Momeni-Varposhti,
Samaneh Khorrami,
Behnam Sadeghi,
Reza Falak
Publication year - 2022
Publication title -
iranian journal of allergy, asthma and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.357
H-Index - 25
eISSN - 1735-5249
pISSN - 1735-1502
DOI - 10.18502/ijaai.v21i2.9224
Subject(s) - ex vivo , tumor infiltrating lymphocytes , cytokine , foxp3 , immune system , cancer research , medicine , triple negative breast cancer , in vivo , tumor microenvironment , flow cytometry , breast cancer , pentoxifylline , regulatory t cell , immunology , immunotherapy , cancer , t cell , biology , il 2 receptor , microbiology and biotechnology
Triple-negative breast cancer (TNBC) is the most aggressive type of BC with the highest percentage of tumor-infiltrating lymphocytes (TILs). Hence, TIL therapy is considered a promising approach to target TNBC. Depletion of regulatory T cells (Tregs) in TILs can improve the antitumor function of TIL therapy. Pentoxifylline (PTXF) is a xanthine derivative that can modulate the nuclear factor kappa B (NF-κB) signaling and probably affect the Treg proportion in TILs. We aimed to evaluate the ex vivo effect of PTXF on the proportion of Treg cells in the TILs derived from a mouse model of TNBC.
The 4T1 cells were inoculated subcutaneously to BALB/c mice to induce TNBC. TILs were isolated from tumor tissue by enzymatic digestion and cultured alone or with 4T1 cells for 24, 48, and 72 h in the presence of interleukin (IL)-2 and different concentrations of PTXF. The toxicity of PTXF and its effects on Tregs proportion as well as cytokine production was evaluated using MTT assay, flow cytometry, and ELISA, respectively.
PTXF had no significant impact on the viability of TILs. Both 500 and 1000 mg/mL of PTXF decreased the proportion of Tregs in a dose-dependent manner. The level of interferon-g and tumor growth factor-b in TILs supernatant were increased and decreased, respectively.
Our data suggest that ex vivo treatment of TILs with pentoxifylline could decrease the proportion of Tregs in the conventional IL-2-mediated TIL expansion and change the cytokine balance of TILs in favor of antitumor immune response.