Role of Diospyros peregrina fruit preparation in suppressing regulatory T (Treg) cells in the tumor microenvironment of breast and lung cancer

Abstract

BackgroundThe most frequent cancers in the world are breast cancer and lung cancer. Regulatory T cells (Treg) are the subtype of T cells that promotes equilibrium between immunological surveillance and immune tolerance, and they are commonly found in high amounts within tumours. The presence of Treg cells in the tumour microenvironment results in immune suppression, due to which immune cells are not able to kill the tumour cells. Diospyros peregrina (Gaertn.) Gürke is an ethnomedicinal plant with hypoglycaemic, diuretic, and anti-cancer effects. This genus, Diospyros, is native to India but distributed throughout the tropics and is characterized by its ability to produce triterpenes of the lupine series and various other bioactive compounds. Diospyros peregrina fruit preparation (DFP) substantially increases tumour protective immunity by suppressing Treg cells. PurposeThis project aims to suppress the regulatory T cells in the tumour microenvironment by giving Diospyros peregrina fruit preparation (DFP) treatment to Treg cells, which will help in controlling and combating breast cancer and lung cancer. MethodFor this project's work, we isolated peripheral blood mononuclear cells from the blood, and the isolated peripheral blood mononuclear cells were used to isolate CD4+CD25+ Treg cells. Then, Diospyros peregrina fruit preparation (DFP) was prepared, which was used to treat CD4+CD25+ Treg cells. Lactate dehydrogenase (LDH) assays, enzyme-linked immunosorbent assays (ELISA), and RT-qPCR were used to determine the effect of DFP treatment on Treg cells. ResultDiospyros peregrina fruit preparation (DFP) treatment suppresses the expression of CD4+CD25+ Foxp3+Treg cells within tumours. DFP-treated CD4+CD25+Foxp3+ Treg cells increase the cytotoxicity within the tumours compared to non-treated Treg cells. DFP treatment help in reducing the release of (T helper type 2) TH2 cell cytokines (Interleukin-10) IL-10 as well as (Interleukin-4) IL-4 and escalating the release of (T helper type 1) TH1 cell cytokines (Interleukin-12) IL-12 and (Interferon-γ) IFN-γ, it also increases the transcriptional activity of T-box transcription factor TBX21 (TBX21) and reduces the expression of the transcription factor FOXP3 and GATA3. ConclusionDiospyros peregrina fruit preparation (DFP) treatment augments the expressions of TH1-specific cytokines and transcription factors, and DFP treatment diminishes the expressions of both TH2 and Treg-specific cytokines and transcription factors.