A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma.

BACKGROUND: Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. METHODS: The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. RESULTS: In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25- T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. CONCLUSIONS: The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression.

Adoptive cell therapy of tolerogenic dendritic cells as inducer of regulatory T cells in allergic rhinitis.

BACKGROUND: Regulatory T cells (Tregs) have become promising candidates for immunotherapy in allergic rhinitis (AR). The contributing role of tolerogenic dendritic cells (tDCs) in the augmentation of Tregs in AR remains to be determined. METHODS: The properties of tDCs in expanding Tregs and their potential to ameliorate AR were evaluated in vitro and in vivo. RESULTS: Monocyte-derived tDCs stimulated with Dermatophagoides pteronyssinus allergen 1 favored the generation of activated Tregs (aTregs) and suppressed effector T-cell responses in a transforming growth factor-beta/interleukin-10 (TGF-ß/IL-10)-dependent manner in vitro. The adoptive transfer of tDCs inhibited allergic airway inflammation in the mouse model, whereas depletion of CD25+ cells or blocking TGF-ß/IL-10 signaling eliminated the inhibitory effect, indicating that Tregs were involved in the anti-inflammatory activity of tDCs. CONCLUSION: Our data show that tDCs are a potential therapeutic target in AR.

Eliciting cytotoxic T lymphocytes against human laryngeal cancer-derived antigens: evaluation of dendritic cells pulsed with a heat-treated tumor lysate and other antigen-loading strategies for dendritic-cell-based vaccination.

BACKGROUND: Dendritic cells (DCs) have been used successfully in clinical pilot studies. However, tumor-specific immunity and clinical responses were only induced in certain cancer patients. It has been well documented that immunotherapy efficacy can be optimized for responses using antigen pulsing. METHODS: The human laryngeal squamous cell cancer (LSCC) cell line SNU899 was used to evaluate the in vitro anti-tumor efficacy of three different preparations of dendritic cell (DC) vaccines consisting of either whole tumor cells or their derivatives including: i) DCs pulsed with a tumor cell supernatant (DC-TCS), ii) DCs pulsed with whole-cell tumor stressed lysate (DC-TSL), and iii) DCs pulsed with irradiated tumor cells (DC-ITC). RESULTS: Our results showed that DC-TSL is an effective source of tumor-associated antigens (TAAs) for pulsing DCs. DC-TSL induced the highest expansion of TAA-specific T cells, the strongest Th1 cytokine response, and the most potent cytotoxic T lymphocyte (CTL) activity. DC-TCS and DC-ITC inhibited T cell activation but induced a certain extent of CTL activity. CONCLUSIONS: These data suggest that DC-TSL is a more potent inducer of antitumor immunity against laryngeal cancer than other antigen-loading strategies using whole tumor cell materials. This strategy provides an alternative approach for DC-based immunotherapy for laryngeal cancer.