2026-10-12T04:43:26Z https://www.scidb.cn/oai

10.57760/sciencedb.012nf 2026-09-16T16:46:15Z

2026-09-16 A CANCER-TO-MACROPHAGE METABOLIC CIRCUIT SHAPES IMMUNOSUPPRESSION IN CCRCC doi:10.57760/sciencedb.012nf en Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is characterized by profound metabolic reprogramming and a highly immunosuppressive tumor microenvironment. Although immune checkpoint blockade (ICB) has substantially improved the treatment of advanced ccRCC, only a subset of patients achieve durable clinical benefit, while primary and acquired resistance remain major therapeutic challenges. Increasing evidence suggests that tumor-intrinsic metabolic alterations not only support cancer cell growth and survival but also profoundly influence the composition and functional state of surrounding immune cells. However, the metabolic determinants that coordinate tumor–immune communication and contribute to immunotherapy resistance in ccRCC remain incompletely understood.Lipid metabolic reprogramming is a prominent feature of ccRCC and is closely associated with tumor progression and immune regulation. Alterations in phospholipid synthesis, remodeling, and intercellular lipid transfer may provide an important mechanism through which malignant cells reshape the tumor immune microenvironment. To identify metabolic regulators involved in ccRCC progression and antitumor immunity, we performed an in vivo CRISPR/Cas9 screening strategy and identified lysophosphatidylcholine acyltransferase 3 (LPCAT3) as a candidate regulator associated with tumor growth and therapeutic response. LPCAT3 is markedly upregulated in ccRCC and its elevated expression is associated with unfavorable clinical outcomes. ccRCC; immunotherapy resistance; phospholipid metabolism Daojia Miao Diaoyi Tan Xiaoping Zhang RESTRICTED dataset Science Data Bank