Li et al. explored in vitro and in vivo the mechanism by which HMGB1 promotes immune escape in renal cell carcinoma (RCC) and found that HMGB1 promotes differentiation and proliferation of myeloid-derived suppressor cells – critical contributors to immunosuppression in RCC – supporting evaluation of anti-HMGB1 or other anti-MDSC therapies.

Despite high immunogenicity and marked presence of immune cells in the RCC(renal cell carcinoma), immunotherapy fails to develop effective anti-tumor immune responses. This is due to the negative regulatory factors in the tumor microenvironment. As the main contributor of immunosuppression, myeloid-derived suppressor cells (MDSCs) inhibited anti-tumor immunity and promoted tumor progression. Meanwhile, it is confirmed that high mobility group box-1 protein (HMGB1) shows a high expression in many solid tumors and HMGB1 with high expression is involved in tumor immune escape. However, the mechanisms linking HMGB1 with tumor immune escape are unclear. The present study aimed to explore whether HMGB1 can promote RCC immune escape by inducing the generation of MDSCs. In this study, Renca mouse model was established and the influence of HMGB1 on MDSCs was investigated by using HMGB1 antibody to downregulate the expression of HMGB1 in tumor-bearing mice. The result showed that with the down-regulation of HMGB1, the tumor growth was inhibited significantly and the mice survival was prolonged greatly. Furthermore, the differentiation and proliferation of MDSCs were inhibited both in vitro and in vivo, and the inhibition rate showed a positive correlation with the degree of down-regulation of HMGB1. When MDSCs were eliminated with Gr-1 antibody in vivo, the ability of the HMGB1 to promote tumor growth was severely impaired. Thus, our findings indicated that HMGB1 might mediate tumor immune escape by promoting MDSCs cell proliferation, which provided a novel theoretical basis for preventing RCC using HMGB1 as the target.

Author Info: (1) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (2) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzho

Author Info: (1) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (2) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (3) Department of Urology, Zhongshan Hospital and School of Basic Medical Sciences, Fudan University, Shanghai, China. (4) Department of Urology, Zhongshan Hospital and School of Basic Medical Sciences, Fudan University, Shanghai, China. (5) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (6) Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (7) Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (8) Department of Digestive Diseases, Huashan Hospital and Biotherapy Research Center, Fudan University, Shanghai, China.