Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-08-28 DOI:10.1016/j.annonc.2025.08.007

B I Rini, L Albiges, X Tang, H Koeppen, A Bex, C Suárez, R Uzzo, H Hamidi, Z J Assaf, S Dubey, E T Goluboff, C Carter, S K Pal, R Banchereau, W Xu, M A Huseni

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引用次数: 0

Abstract

Background: Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma.

Patients and methods: Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated. This trial did not meet its primary DFS endpoint in the intention-to-treat population. An affinity-based proximity extension proteomics assay was used to compare levels of circulating proteins among baseline (post-nephrectomy) serum samples and samples taken at time of recurrence.

Results: Serum KIM-1 was the most significantly enriched protein at recurrence versus baseline. Patients with serum KIM-1^high at baseline had worse disease-free survival (DFS) (hazard ratio 1.68, 95% CI 1.35-2.09), but also had improved DFS when treated with adjuvant atezolizumab versus placebo (hazard ratio 0.72, 95% CI 0.52-0.99). An increase in KIM-1 during follow-up was associated with worse DFS compared to patients with no increase in KIM-1. Within the KIM-1 high subgroup, longer DFS following atezolizumab treatment was associated with increased baseline expression of T effector and Th1 signatures, while shorter DFS was associated with increased baseline expression of matrix remodeling genes and protumor cytokines.

Conclusion: These analyses suggest that elevated post-nephrectomy plasma KIM-1 level and kinetics are prognostic, supporting the hypothesis that KIM-1 is a biomarker for minimal residual disease in RCC. As KIM-1^high patients are also enriched for benefit from adjuvant immunotherapy, biomarker driven adjuvant therapy should be evaluated as a potential new paradigm in RCC.

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肾细胞癌中循环肾损伤分子-1 （KIM-1）及其与辅助免疫治疗结果的关系

背景：辅助免疫治疗是目前切除肾细胞癌（RCC）复发风险增加患者的标准治疗，但没有生物标志物可用于指导治疗。肾损伤分子-1 （KIM-1）先前被描述为肾细胞癌中潜在的循环生物标志物。患者和方法：参与一项随机III期试验的患者的生物标志物和结果进行了评估，该试验是在切除的RCC （IMmotion010）中进行的辅助atezolizumab与安慰剂的对比。该试验在意向治疗人群中未达到其主要DFS终点。采用基于亲和的邻近扩展蛋白质组学分析来比较基线（肾切除术后）血清样本和复发时样本的循环蛋白水平。结果：与基线相比，血清KIM-1是复发时最显著的富集蛋白。基线时血清kim -1高的患者无病生存期（DFS）较差（风险比1.68,95% CI 1.35-2.09），但与安慰剂相比，阿特唑单抗辅助治疗也改善了DFS（风险比0.72,95% CI 0.52-0.99）。与KIM-1未升高的患者相比，随访期间KIM-1升高与更差的DFS相关。在KIM-1高亚组中，atezolizumab治疗后较长的DFS与T效应和Th1特征的基线表达增加有关，而较短的DFS与基质重塑基因和肿瘤细胞因子的基线表达增加有关。结论：这些分析表明，肾切除术后血浆KIM-1水平和动力学升高与预后有关，支持了KIM-1是肾癌最小残留病变生物标志物的假设。由于kim -1高患者也可以从辅助免疫治疗中获益，生物标志物驱动的辅助治疗应该作为RCC的潜在新范式进行评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.