Myeloid derived suppressor cells (MDSCs) expand in cancer bearing hosts and contribute to tumor immune evasion. M2 macrophages constitute a major cellular component of cancer-related inflammation. However, the correlation between circulating MDSCs and infiltrating M2 macrophages in tumor tissues from patients with esophageal cancer (ECA), and its potential relationship with the polarization of Th2 cells remain unclear. In the present study, we showed the level of MDSCs in PBMC and Arg1 in plasma were significantly elevated in ECA patients, and the increased ratio of MDSC in PBMC was closely related to the expression of CD163 in cancer tissues. In addition, the ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3, as well as the protein levels of IL-13 and IL-6, but IFN-γ and IL-12 in peripheral blood were decreased. Our data indicate that the increased Th2 cytokines are associated with MDSCs and M2 macrophages polarization, and foster the infiltration of CD163+M2 macrophages in cancer tissues, which promote the formation of immunosuppressive microenvironment in ECA patients.

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Upregulated high-mobility group box 1 (HMGB1) has been found in many diseases. Nevertheless, the function of HMGB1 on modulating the proliferation of lung cancer cells (Lewis cells) and inhibiting apoptosis is poorly understood, as well as the involved intracellular signalling. In the present study, we firstly found the apoptosis of Lewis was increased following Hanks' balanced salt solution (HBSS)-induced starvation, while it was rescued after exogenous HMGB1 protein was added; furthermore, the receptor for advanced glycation end products (RAGE) and Toll-like receptor (TLR4) could coordinately improve the proliferation of tumour cells in vitro, and HMGB1 could enhance the phosphorylation of PI3K/Akt and Erk1/2, inhibit the expression of pro-apoptosis protein Bax and promote the expression of anti-apoptosis protein Bcl-2. These findings clearly demonstrated that HMGB1-RAGE/TLR4-PI3K-Akt/Erk1/2 pathway contributed to the proliferation of Lewis. Moreover, our observations provide experimental and theoretical basis for clinical biological therapy for cancers; it also may be a new target for intervention and treatment of lung cancer.