A highly branched α-D-glucan facilitates antitumor immunity by reducing cancer cell CXCL5 expression

Tumor immunotherapy has emerged as a major pillar of anticancer therapeutic strategies. Natural polysaccharides, known for their strong immunomodulatory activities with relatively low cost and toxicity, are becoming promising prospects for cancer immunotherapy. In this study, we investigated the antitumor mechanism of JNY2PW, a highly branched α-d-glucan previously purified from the traditional marine Chinese medicine Arca inflata . JNY2PW was shown to enhance the sensitivity of tumor cells to co-culture macrophage supernatants by decreasing cancer cell CXCL5 expression. Furthermore, JNY2PW exerted antitumor effects without obvious toxic side effects in tumor-bearing mice by triggering the Akt/mTOR and ERK/GSK3β/β-catenin pathways and attenuating expression of CXCL5 in cancer cells. Remarkably, JNY2PW reduced tumor proliferation and dampened CXCL5 expression in tumor cells overexpressing CXCL5 both in vitro and in vivo . Additionally, JNY2PW blocked epithelial-mesenchymal transition (EMT) in both CXCL5-overexpressing and wild type tumor cells. Our data therefore uncovered a previously unrecognized antitumor mechanism for JNY2PW, suggesting that JNY2PW is a promising adjuvant as an immunomodulator for cancer immunotherapy. • A new branched α -d-glucan, JNY2PW, enhanced the sensitivity of tumor cells to cocultured macrophage supernatants. • JNY2PW exerted antitumor effects without obvious toxic side effects in tumor-bearing mice. • JNY2PW decreased expression of CXCL5 in cancer cells by triggering the Akt/mTOR and ERK/GSK3β/β-catenin pathways. • JNY2PW shows great potential as an immunomodulator for cancer immunotherapy.