缺乏对免疫检查点抑制（ICI）反应的可靠预测生物标志物。治疗前血清白蛋白是 ICI 治疗患者的已知预后和预测因素，已被提议作为抗 PD1/PD-L1 抗体的潜在药代动力学替代标志物，因为它与 IgG 共享稳态途径。然而，这一假设目前基于理论考虑和回顾性数据的有限证据。因此，我们全面研究了预处理白蛋白的预后和预测价值及其与抗PD-L1 IgG水平的关系。我们分析了患者的四项试验（IMvigor210、IMvigor211、IMmotion151和OAK）中的预处理白蛋白和atezolizumab血清水平以及临床反应患有转移性肺癌、肾癌或尿路上皮癌且单独或联合接受阿替利珠单抗治疗的患者。总共分析了 3391 名患者。血清白蛋白和阿替利珠单抗水平之间的相关性较弱（皮尔逊系数 0.23）。我们发现在所有试验中预处理血清白蛋白都具有很强的预后价值。阿特珠单抗血清水平和血清白蛋白均与总生存期独立相关。重要的是，在三项随机 III 期临床试验中，与活性比较组相比，免疫治疗的生存获益仅限于治疗前血清白蛋白 > 35 g L-1 的患者。我们的数据不支持白蛋白作为替代物的假设用于 atezolizumab 药代动力学。然而，我们表明白蛋白本身对接受免疫治疗的患者具有很强的预后价值。由于免疫治疗的获益仅限于血清白蛋白水平正常/升高的患者，因此基线白蛋白有可能用作免疫检查点抑制的预测标记。© 2023 作者。临床

Reliable predictive biomarkers for response to immune checkpoint inhibition (ICI) are lacking. Pretreatment serum albumin, a known prognostic and predictive factor in ICI-treated patients, has been proposed as a potential pharmacokinetic surrogate marker for anti-PD1/PD-L1 antibodies, as it shares a homeostatic pathway with IgG. However, this hypothesis is currently based on theoretical considerations and limited evidence from retrospective data. Therefore, we comprehensively investigated the prognostic and predictive value of pretreatment albumin and its relationship with anti-PD-L1 IgG levels.We analysed pretreatment albumin and atezolizumab serum levels and clinical response in four trials (IMvigor210, IMvigor211, IMmotion151 and OAK) of patients with metastatic lung-, renal- or urothelial cancer who received atezolizumab alone or in combination.A total of 3391 patients were analysed. Correlation between serum albumin and atezolizumab levels was weak (Pearson's coefficient 0.23). We found a strong prognostic value for pretreatment serum albumin across all trials. Both atezolizumab serum levels and serum albumin were independently correlated with overall survival. Importantly, in the three randomised phase III clinical trials, the survival benefit for immunotherapy compared with the active comparator arm was limited to patients with pretreatment serum albumin > 35 g L-1.Our data do not support the hypothesis that albumin serves as a surrogate for atezolizumab pharmacokinetics. However, we show that albumin on its own exerts strong prognostic value for patients treated with immunotherapy. As benefit from immunotherapy was limited to patients with normal/elevated serum albumin levels, baseline albumin could potentially be used as a predictive marker for immune checkpoint inhibition.© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.