Lycium barbarum L. polysaccharide LBP3 exerts the anti-tumor effect through enhancing the function of tumor-associated dendritic cells via inhibiting IRE1-XBP1 pathway of ER stress

Liver cancer is a huge global challenge. It has been exacerbated by tumor-associated dendritic cells (TDCs) due to Endoplasmic Reticulum (ER) stress. We planned to investigate the effects of LBP3 on TDCs immune function, and to explore whether the underlying mechanism was associated with IRE1 alpha-XBP1 pathway of ER stress regulating lipid metabolism. In our early studies, LBP3 (40-350 kDa) with significant anti -tumor and immunomodulatory activities was isolated from the polysaccharide of Lycium barbarum L. (LBP). Here, we determined that LBP3 had a great anti -tumor efficacy in H22 -tumor bearing mice by functional activation of TDCs. In vivo and in vitro results showed that LBP3 could up-regulate the expression of MHC II, CD80 and CD86 on TDCs, increase the level of TNF-alpha secreted by TDCs, enhance TDCs' ability to improve the proliferation and immunosuppression of lymphocytes. Furthermore, LBP3 could decrease the high expression of ER stress-related proteins IRE1 alpha, GRP78, XBP1 and CHOP, reduce the lipid accumulation, raise the low expression of costimulatory molecules on TDCs induced by thapsigargin (TG). Taken together, LBP3 could reduce intracellular lipid accumulation by inhibiting IRE1 alpha-XBP1 pathway of ER stress, improve the function of TDCs to stimulate T cells, thence play an anti -tumor role.