Actinidia eriantha polysaccharide prevents gastric cancer invasion and metastasis via inhibition of PD-1/PD-L1 regulation of macrophage polarization

Actinidia eriantha polysaccharide (AEPS), an active component of the Chinese herbal medicine Radix Actinidia chinensis, has anticancer effects. Here, we investigated the therapeutic potential of AEPS in gastric cancer through in vivo, in vitro, and in silico analyses. In our gastric cancer xenograft mouse model, AEPS effectively reduced tumor volume and weight. In the human gastric adenocarcinoma cell line AGS, AEPS inhibited migration and invasion without affecting proliferation; this result was validated in a fluorescent-labeled lung metastasis mouse model. Mass cytometry revealed that AEPS enhanced macrophage proportions in gastric cancer tissues. Bioinformatics analysis revealed a strong increase in PD-1-regulated M2 macrophage proportions in patients with gastric cancer, shortening their survival time and worsening their prognosis. In the coculture system of interleukin-4-induced human monocytic leukemia cells and AGS cells, AEPS treatment downregulated PD-1/PD-L1 and M2 macrophage-related marker expression but promoted TAM polarization toward the M1 phenotype. These findings facilitated the elucidation of the mechanism underlying the treatment effects of AEPS against gastric cancer. Finally, AEPS-PD-1 antibody combination therapy further enhanced the anticancer effects of AEPS in vivo, suggesting its potential as a basis to develop novel therapeutics for gastric cancer.