Nature Cancer：张金方/雷晓光等发现癌症免疫治疗新靶点——CDK10

Core Viewpoint - Cancer immunotherapy has transformed cancer treatment, but many patients do not respond. Activating innate immunity presents a promising method to enhance treatment efficacy, yet the specific signal kinases involved remain largely unknown [3]. Group 1: Research Findings - A recent study published in Nature Cancer identified CDK10 as a key driver of immune evasion in cancer cells, which suppresses antitumor immunity by limiting the production of immunostimulatory nucleic acids [3][4]. - The research utilized in vivo CRISPR screening to establish CDK10 as a critical inhibitory factor in tumor immune surveillance [4]. - CDK10 reduces the accumulation of double-stranded RNA and R-loops by phosphorylating DNMT1 and RAP80, thereby dampening the activation of innate immune pathways mediated by MDA5 and cGAS [4]. Group 2: Clinical Implications - The study confirmed that lower expression levels of CDK10 in tumors correlate with better responses to immunotherapy in cancer patients [5]. - These findings position CDK10 as a significant regulatory factor in tumor immunity and a potential therapeutic target [6]. Group 3: Related Commentary - A commentary published alongside the study in Nature Cancer highlighted that the activation of cytoplasmic nucleic acid sensors in tumor cells is a crucial early step in initiating antitumor immunity, although the mechanisms controlling their activity are not fully understood [6].