免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Serum Arginase-1 is a predictive biomarker for melanoma patients and a surrogate indicator of systemic myeloid cell fitness.
Serum Arginase-1 is a predictive biomarker for melanoma patients and a surrogate indicator of systemic myeloid cell fitness.
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尽管免疫肿瘤学的最新进展已经彻底改变了癌症治疗,但只有一部分患者从这些治疗中获益并获得持久的临床缓解。基于生物标志物指导识别可能对免疫治疗有反应的患者,可能有助于更有效地管理各种恶性肿瘤。为了探索这一点,我们利用了一项I期试验,该试验评估了抗原工程化树突状细胞(DC)疫苗在促进黑色素瘤患者抗肿瘤免疫方面的疗效,该疫苗分别作为单药治疗或与高剂量干扰素-α2b联合给药。此前,已使用Luminex、NanoString基因表达谱分析和流式细胞术对液体活检,包括血清和外周血单个核细胞,以及肿瘤活检进行了预测标志物分析。在这里,进行了体外刺激试验,以评估循环髓系亚群产生精氨酸酶-1的情况。在73种血清分析物中,血清精氨酸酶-1(sArg1)最能有效区分可测量疾病的黑色素瘤患者与健康供者。活动性疾病患者中sArg1水平升高与对疫苗的良好反应相关,并与更长的总生存期和无进展生存期相关。整合的表型、功能和代谢分析确定循环CD14 - CD11c + DC3可能是sArg1的来源。这些发现支持以下假设:sArg1可能作为癌症疫苗免疫治疗反应性的生物标志物,并反映与增强抗肿瘤免疫相关的全身髓系细胞适应性。鉴于血清相较于细胞或组织具有稳定性和可及性,该检测可能提供一种评估患者状态的方法,从而可能改善分层和临床决策。
While recent advances in immuno-oncology have revolutionized cancer therapy, only a subset patients benefit from these treatments and achieve durable clinical responses. Biomarker-guided identification of patients likely to respond to immunotherapy could enable more effective management of various malignancies.
To explore this, we took advantage of a Phase I trial evaluating the efficacy of antigen-engineered dendritic cell (DC) vaccine, administered either as monotherapy or in combination with high-dose interferon-α2b, in promoting anti-tumor immunity in melanoma patients. Liquid biopsies, including serum and peripheral blood mononuclear cells, and tumor biopsies were previously analyzed for predictive markers using Luminex, NanoString gene expression profiling and flow cytometry.
Here, in vitro stimulation assays were conducted to assess arginase-1 production by circulating myeloid subsets. Of 73 serum analytes, serum arginase-1 (sArg1) most effectively distinguished melanoma patients with measurable disease from healthy donors. Elevated sArg1 levels in patients with active disease correlated with favorable responses to the vaccine and were associated with longer overall and progression-free survival. Integrated phenotypic, functional and metabolic analyses identified circulating CD14 - CD11c + DC3 as the likely source of sArg1.
These findings support the hypothesis that sArg1 may serve as a biomarker for responsiveness to cancer vaccine immunotherapy and reflect systemic myeloid cell fitness associated with enhanced anti-tumor immunity. Given the stability and accessibility of serum compared to cells or tissues, this assay could offer a method for assessing patient status, potentially improving stratification and clinical decision-making.
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