BACKGROUND: Due to their potent immunomodulatory effects, herbal polysaccharides, are used as immunomodulators in combination with other anti-tumor therapies, demonstrate potential in the treatment of tumors. METHODS: In this paper, we simulated the immune cycle of immunogenic cell death (ICD) in vitro to investigate the regulatory mechanism of four different polysaccharides-mediated "immuno-photothermal" combination therapies on the immune cycle of ICD, and validated it in vivo. RESULTS: The experimental results showed that the combination therapy strategies mediated by four different polysaccharides (excluding Poria cocos mushroom polysaccharides) could significantly increase the expression and release of ICD markers in tumor cells (4 T1), which was conducive to enhancing the "immune starting point" of ICD. For the "immune line/bridge", four different polysaccharides-mediated combination therapies significantly increased the number and percentage of mature dendritic cells (DCs) and promoted the proliferation and migration of DCs. For the "immune ending point", the number, proliferation, and migration recruitment of CD3 CONCLUSIONS: All four polysaccharides can positive modulate the dynamic process of the immune cycle and enhance anti-tumor efficacy. Highlighting the crucial role and mechanism of polysaccharides in combination therapy. Providing new ideas and rationale for polysaccharide-mediated anti-tumor combination therapy.