1172-Hypoxia-Driven Therapeutic Response in Metastatic ccRCC

This research examines how intratumoral hypoxia dictates the effectiveness and eventual resistance of VEGFR-TKI and immunotherapy combinations in clear cell renal cell carcinoma. By utilizing both transgenic mouse models and human patient cohorts, the authors discovered that while these treatments initially trigger beneficial tumor necrosis, prolonged exposure can paradoxically drive metastatic progression. A specific population of SPP1+ macrophages was identified as a critical indicator of true tissue hypoxia, serving as a biological proxy for therapeutic response. The study further highlights a functional dichotomy between different macrophage types, noting that while some are necessary for immune-mediated control, others emerge during chronic treatment to signal emerging resistance. Ultimately, the research suggests that monitoring hypoxia-driven remodeling is essential for refining treatment strategies and predicting patient outcomes in advanced kidney cancer.References:Vuong L, Cornish AE, Pfeil J, Khandwala Y, Jiang H, Zheng DXT, Mascareno EA, Rittenhouse N, Rappold PM, Leibold J, Sabio EA, Weiss K, Gonzalez C, Ji L, Zhang J, Adlesic M, Akin O, Flynn J, Krishna C, Lopez Sanmiguel A, Sager RA, Tan TJ, Sanchez A, Di Natale RG, Blum KA, Russo P, Coleman JA, Frew IJ, Chowell D, Chen YB, Solit DB, Ostrovnaya I, Motzer RJ, Voss MH, Kotecha RR, Chan TA, Jackson HW, Kuo F, Li MO, Hakimi AA. Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma. Cancer Cell. 2026 Jun 4:S1535-6108(26)00252-7. doi: 10.1016/j.ccell.2026.05.007. Epub ahead of print. PMID: 42242232.前往小宇宙评论区与主播互动