Efficacy of selective renal tumor embolization combined with axitinib and reduced-dose toripalimab in oligometastatic clear cell renal carcinoma: An updated analysis with patient-derived organoid and immune co-culture insights.

Abstract

495 Background: Oligometastatic clear cell renal cell carcinoma (ccRCC) presents an opportunity for aggressive local and systemic therapy. Combining selective renal tumor embolization with targeted therapy and immunotherapy is a promising strategy. We further established a patient-derived organoid (PDO) platform co-culturing ccRCC cells with immune cells to investigate its predictive value and the mechanism underlying treatment efficacy. Methods: This study included oligometastatic ccRCC patients treated since March 2023. Patients were propensity-score matched into two groups: the experimental group received selective renal tumor embolization, axitinib (5 mg BID), and reduced-dose toripalimab (160 mg Q3W); the control group received axitinib plus standard-dose toripalimab (240 mg Q3W). Primary outcomes were DCR, ORR, and 1-year PFS. Secondary outcomes included grade 3-4 AEs. A novel PDO model co-culturing patient-derived ccRCC cells with autologous immune cells was established to simulate the tumor microenvironment. Results: After matching (29 patients per group), baseline characteristics were balanced. The experimental group showed significantly superior DCR (100% vs. 69.8%, P < 0.05), ORR (93.1% vs. 56.7%, P < 0.05), and 1-year PFS rate (92.8% vs. 67.9%). Grade 3-4 AEs were lower in the experimental group (10.1% vs. 38.4%, P < 0.05). In vitro , the PDO-immune co-culture model demonstrated that hypoxia – mimicking post-embolization conditions – effectively increased the infiltration ratio of CD8+ T cells within the organoid. This remodeled immune microenvironment significantly enhanced the tumor-killing efficacy of axitinib combined with toripalimab. Conclusions: The combination of selective renal tumor embolization with axitinib and reduced-dose toripalimab yields significantly improved clinical outcomes and reduced toxicity in oligometastatic ccRCC. Our pioneering PDO-immune co-culture platform reveals that hypoxia-induced CD8+ T cell infiltration may be a key mechanism, positioning this model as a promising predictive biomarker for treatment response. These findings warrant further validation in larger prospective studies.