Antitumor effect of a polysaccharide from Pseudostellaria heterophylla through reversing tumor-associated macrophages phenotype

Tumor-associated macrophages (TAMs), which are predominant tumor-infiltrating immune cells in the tumor microenvironment, participate in promoting the occurrence and metastasis of tumor cells. Reprogramming TAMs has become a promising immunotherapeutic approach for novel cancer treatments. In this study, a homogeneous polysaccharide (PHP-1) was obtained from Pseudostellaria heterophylla, and its antitumor and immunological activities, as well as the underlying molecular mechanisms were explored. These findings suggested that PHP-1 can switch M2 macrophages to the M1 type, thereby promoting tumor cell apoptosis in vitro. In addition, PHP-1 can modulate the TAMs phenotype, maintain the CD4+/CD8+ lymphocyte balance, and exert antitumor effects in H22 tumor-bearing mice. Mechanistically, PHP-1 is recognized by the TLR4 receptor, promotes Ca2+ release, and activates the NF-κB and MAPK signaling pathways to reset the M2-type macrophages. These findings indicate that PHP-1 from P. heterophylla can function as a tumor immunotherapeutic modulator.