Rhodium(III)\nComplex Noncanonically Potentiates Antitumor\nImmune Responses by Inhibiting Wnt/β-Catenin Signaling

Metal-based chemoimmunotherapy has recently garnered\nsignificant\nattention for its capacity to stimulate tumor-specific immunity beyond\ndirect cytotoxic effects. Such effects are usually caused by ICD via\nthe activation of DAMP signals. However, metal complexes that can\nelicit antitumor immune responses other than ICD have not yet been\ndescribed. Herein, we report that a rhodium complex (<b>Rh-1</b>) triggers potent antitumor immune responses by downregulating Wnt/β-catenin\nsignaling with subsequent activation of T lymphocyte infiltration\nto the tumor site. The results of mechanistic experiments suggest\nthat ROS accumulation following <b>Rh-1</b> treatment is a critical\ntrigger of a decrease in β-catenin and enhanced secretion of\nCCL4, a key mediator of T cell infiltration. Through these properties, <b>Rh-1</b> exerts a synergistic effect in combination with PD-1\ninhibitors against tumor growth <i>in vivo</i>. Taken together,\nour work describes a promising metal-based antitumor agent with a\nnoncanonical mode of action to sensitize tumor tissues to ICB therapy.