Supplementary file 1_Astragalus polysaccharide antagonized anti PD-1 efficacy in melanoma through inhibiting JAK-STAT1/CIITA and TLR/NF-κB signaling.docx

APS reversed anti PD-1-induced infiltration of CD4⁺ T cells, CD8⁺ T cells and dendritic cells (DCs) in the tumor microenvironment, and impaired DC maturation and CD4⁺ T cell activation. Mechanistically, APS significantly inhibited JAK-STAT1 signaling, downregulated MHCII master regulator CIITA, and subsequently reduced MHCII expression. Meanwhile, APS markedly suppressed TLR signaling and attenuated NF-κB mediated inflammatory responses in B16-OVA melanoma cells and DCs.</p>Conclusion<p>APS antagonized anti PD-1 efficacy by inducing an immunosuppressive microenvironment via dual inhibition of JAK-STAT1/CIITA signaling and TLR/NF-κB signaling.

This study suggests that the combination of natural polysaccharides and ICIs may warrant caution, although further studies are needed to validate these findings and determine their clinical relevance.</p>