Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/β-Catenin Signaling

作者：Feng-Yang Wang, Liang-Mei Yang, Xiaolin Xiong, Jing Yang, Yan Yang, Jiu-Qin Tang, Lei Gao, Yuan Lu, Yuan Wang, Taotao Zou, Hong Liang, Ke-Bin Huang · 发表于：Journal of Medicinal Chemistry · 年份：2024 · DOI：10.1021/acs.jmedchem.4c00583 · 被引用次数：13 · 研究领域：Cancer Immunotherapy and Biomarkers、Nanoplatforms for cancer theranostics、Adenosine and Purinergic Signaling

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex ( Rh-1 ) triggers potent antitumor immune responses by downregulating Wnt/β-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in β-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo . Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.