Integrating network pharmacology with ex-vivo analysis to assess the effect of IL-2 in halting breast cancer: involvement of Treg/CTLA-4/Blimp-1/caspase-3

Abstract

The T lymphocytes have a vital role in tumor immunosurveillance within the tumor microenvironment (TME) but on the other hand, the TME adopts several mechanisms that cause inhibition and apoptosis to effector T cells leading to tumor immune evasion. The controversial role of interleukin-2 (IL-2) was demonstrated by promoting the activation and proliferation of different immune cells such as NK cells, effector and regulatory T cells (T regs). Thus, ex-vivo approach was used to investigate IL-2 anti-tumor effect on breast cancer cells isolated from Egyptian patients after mastectomy via modulating Treg/CTLA-4/Blimp-1/caspase-3 trajectory. Previous to the ex-vivo approach we aimed to find common targets between IL-2 and breast cancer disease using network pharmacology. Results of network pharmacology illustrated that there were 35 common targets including CD4, CTLA-4 and caspase 3. Breast cancers cells obtained were then cultured in the presence of 10 µl of (50 ng/ml) recombinant IL-2 for 24 h. Results revealed that tissue culture supplementation with IL-2 significantly reduced T regs within the TME via inhibiting the tumor expression of CD25 and Forkhead box P3 (FOXP3). In addition, it was found that IL-2 significantly decreased the expression of the inhibitory receptor CTLA-4 and increased the expression of B lymphocyte-induced maturation protein-1(Blimp-1), leading to the activation of effector T cells and the induction apoptosis of the breast tumor cells. These findings suggest that IL-2 could serve as a new treatment strategy for breast cancer via modulating immune responses within the TME.