Scheme 1.

Illustration of the combination of CA4-NPs and DC101 enhancing the therapeutic efficacy of anti-PD-1 in HCC. 1) CA4-NPs disrupted the tumor blood vessels, leading to tumor hypoxia, and reduced tumor burden. 2) DC101 normalized the tumor vasculature, reduced tumor hypoxia, and increased the number of intratumoral CD8⁺ T cells. CA4-NPs + DC101 reduced tumor burden, while simultaneously increasing the number of intratumoral CD8⁺ T cells, and regulated the imbalance between CD8⁺ T cells and tumor burden. 3) The synergistic effects of CA4-NPs + DC101 with anti-PD-1 increased the number of intratumoral CD8⁺ T cells and increased the secretion of IFN-γ. In the absence of CA4-NPs + DC101, anti-PD-1 alone showed no significant effects with respect to the activation of CD8⁺ T cells or tumor inhibition.