Effect of TGF‑β1 on blood CD4+CD25high regulatory T cell proliferation and Foxp3 expression during non‑small cell lung cancer blood metastasis

Abstract

Metastatic circulating tumor cells in non-small cell lung cancer (NSCLC) metastasis have been reported to be associated with an immune response. The present study aimed to provide a theoretical basis for the immunomodulatory processes during NSCLC blood metastasis. NSCLC blood and normal peripheral blood mononuclear cells (PBMCs) were collected. The quantity of cluster of differentiation (CD)4CD25 regulatory T (Treg) cells and the intracellular forkhead box protein 3 (Foxp3) expression in CD4CD25 Treg cells were determined by flow cytometry. Furthermore, the effect of transforming growth factor β1 (TGF-β1) on NSCLC blood CD4CD25 Treg cell proliferation was explored by activating blood mononuclear cells with an anti-CD3 monoclonal antibody, interleukin-2 and different doses of TGF-β1. Reverse transcription-quantitative polymerase chain reaction assays were used to detect the mRNA expression of Foxp3. Carboxyfluorescein succinimidyl ester staining was used to analyze the proliferation dynamics of lymphocyte subsets. Results indicate that the proportion of CD4 T cells in the blood of patients with NSCLC was significantly higher compared with normal peripheral blood (P<0.01). Foxp3 expression in NSCLC blood Treg cells was significantly decreased compared with normal peripheral blood (P<0.01). NSCLC blood mononuclear cells treated with TGF-β1 at 1, 5 and 25 ng/ml significantly induced Foxp3 expression in CD4CD25 Treg cells compared with the control group (P<0.05). The proportion of CD4CD25 Treg and CD8 T cells were elevated in generation 6, 7, 8 after 6 days of TGF-β1 treatment compared with untreated cells. The proportion of CD4CD25 Treg and CD8 T cells were elevated in generation 8, 9 and with TGF-β1 treatment after 8 days compared with untreated cells. These results indicate that CD4CD25 Treg cells proliferate at a greater rate compared with CD8 T cells after 4, 6 or 8 days of treatment. The proportion of CD4CD25 Treg cells in NSCLC blood was significantly higher (P<0.05) compared with normal peripheral blood. The number of Foxp3 T cells was significantly lower (P<0.05) compared with normal peripheral blood. The data presented in this study suggest that NSCLC blood CD4CD25 Treg cells are functionally immature and that TGF-β1 may promote maturation.

PLD1 and PLD2 differentially regulate the balance of macrophage polarization in inflammation and tissue injury

“…M2 macrophages promote the differentiation of Foxp3‐positive Tregs (Schmidt et al, 2016; Wynn & Vannella, 2016). TGFβ, secreted by M2 macrophages, increases the differentiation of Foxp3‐positive Tregs (Hu et al, 2018). We found that PLD1‐deficient macrophages showed augmented TGFβ expression in the M2‐polarization condition (data not shown).…”

Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance

“…TGF-β1 inhibited antigen-specific CD8+ T-cell effector functions as demonstrated in melanoma (Ahmadzadeh and Rosenberg, 2005) and increased the number and immunosuppressive capacity of regulatory T cells (Hu et al, 2018;Huber et al, 2004;Marie et al, 2005;Polanczyk et al, 2019).…”

Dendritic cells transfected with a polyepitope DNA construct stimulate an antitumor cytotoxic response in various tumors

“…Hitherto, DNA constructs encoding epitopes of tumor-associated antigens have been successfully used previously (46). The following step in the development of this therapeutic approach is the creation of DNA constructs that can cover a wide range of tumor antigens, which is crucial, considering that the expression of tumor antigens may change qualitatively and quantitatively during chemotherapy and radiation therapy (47).…”