Tumor associated neutrophils governs tumor progression through an IL-10/STAT3/PD-L1 feedback signaling loop in lung cancer

Tumor associated neutrophils governs tumor progression through an IL-10/STAT3/PD-L1 feedback signaling loop in lung cancer

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Tumor-associated neutrophils (TANs) can exist in either a pro-inflammatory or an anti-inflammatory state, known as N1 and N2, respectively.Anti-inflammatory TANs have been shown to correlate with poor prognosis and tumor progression in patients.To Semi-integrated Dishwasher explore the role and mechanisms of TANs in lung cancer development, we isolated neutrophils from both peripheral blood and tumor tissues of patients/mice, and assessed their functional interaction with lung cancer cells both in vitro and in vivo.Our results revealed that tumor-derived neutrophils (or TANs) promote the tumorigenic and metastatic potential of lung cancer cells.Upon tumorigenesis, TANs display a N2-like status and secrete the cytokine IL-10 to facilitate the activation of c-Met/STAT3 signaling, which ultimately enhances distant metastasis in vivo.

Meanwhile, the transcription factor STAT3 increases PD-L1 level in tumor cells, which promotes neutrophils polarization towards a N2-like status, leading to a positive feedback loop between TANs, IL-10, STAT3, PD-L1, and TANs themselves.Blocking IL-10, we additionally eliminated metastatic tumor nodules and enhanced the anticancer effects of chemotherapy in a Lewis mouse model.Our Seasonal Decorations findings suggest a positive feedback loop between tumor cells and TANs that controls tumor progression and patient outcome in lung cancer.