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[摘要] 近年来,免疫检查点抑制剂在肺癌治疗中取得突破性进展,正迅速改变着肺癌的治疗模式,也标志着免疫治疗2.0 时代的到来。新的肿瘤治疗模式对精准医学提出更高要求,对程序性死亡受体1(programmed death 1, PD-1)/程序性死亡配体1(programmed death ligand 1, PD-L1)抑制剂预后生物标志物也在不断地探索之中,主要包括以下几个方面:PD-L1 表达水平、肿瘤基因组异质性与肿瘤新抗原、T细胞特点、肿瘤微环境以及机体整体状态等。本文将针对目前PD-1/PD-L1 抑制剂在肺癌免疫治疗中的潜在生物标志物最新临床研究进展及其研究前景进行综述。 相似文献
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近年来,以免疫检查点为靶点的免疫疗法在多种晚期实体肿瘤中取得了革命性的突破,尽管长期疗效非常显著,但仅限于一小部分肿瘤患者。有些患者会产生耐药及免疫相关不良事件(irAEs)。免疫检查点抑制剂(ICIs)主要包括靶向细胞毒性T淋巴细胞抗原-4的抗体以及靶向程序性细胞死亡受体-1及其配体的抗体。因此,筛选可能受益于免疫疗法人群的潜在生物标志物,以最大程度提高治疗效益是重中之重。本文就ICIs作用机制及其相关疗效生物标志物方面进行综述,以更好地指导免疫治疗在临床中的应用。 相似文献
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程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)免疫检查点抑制剂的发展为非小细胞肺癌(NSCLC)的治疗提供了新的方向.然而,疗效预测标志物的尚未确定在很大程度上限制了其有效应用.本文对美国食品药品监督管理局(FDA)批准、尚处于试验阶段的PD-1/PD-L1抑制剂的相关临床试验进行了综述.事实上,目前仅有约20%的晚期NSCLC患者可以从PD-1/PD-L1抑制剂中获益.多数临床试验将患者的PD-L1表达水平作为疗效预测标志物,但其预测价值不尽相同,本文亦对其临床应用局限性的原因进行了讨论.随着肿瘤突变负荷、肿瘤免疫微环境等新兴标志物的出现,将其与PD-L1表达相结合,指导PD-1/PD-L1抑制剂有效的个体化应用正逐渐成为新的研究方向. 相似文献
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免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)联合化疗在晚期胃癌的临床研究中获得了明显的生存获益,但仍有部分胃癌患者对免疫治疗不敏感,存在免疫耐受现象及发生严重的治疗相关不良反应。如何在晚期胃癌患者中,选择ICIs联合化疗的优势人群是临床上亟需解决的问题。本文就晚期胃癌一线治疗的研究进展,对HER2阳性和HER2阴性的晚期胃癌行PD-1/PD-L1抑制剂联合化疗的疗效相关生物标志物,以及其他潜在的生物标记物分别展开综述,探讨其目前的应用现状及面临的问题、挑战及发展趋势。未来开发多个生物标记物联合评估模式及预测模型的建立可能更准确地确定免疫治疗优势人群。 相似文献
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目前,肿瘤的治疗手段多种多样,具体的治疗方案根据肿瘤分期、性质及患者自身状态而定。而以PD-1/PD-L1抑制剂为基础的免疫治疗疗法引领肿瘤治疗进入了新时代,在多种实体瘤中都取得了巨大成功。临床实践却发现,并非所有的患者都能从免疫治疗中获益,甚至免疫治疗会导致患者病情出现爆发性进展或假性进展。因此,为实现更精准的治疗,减少患者经济损失,提高免疫抑制剂的有效率,探寻合适的疗效预测标志物来筛选可受益的患者成为了临床重要的研究热点和迫切需求。免疫疗法拥有巨大的应用潜力,筛选其疗效预测标志物对预后分层、辅助诊断、药物选择等方面具有重要的意义。为进一步指导临床,本文就PD-1/PD-L1抑制剂的疗效标志物作出系统综述。 相似文献
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随着免疫检查点抑制剂(immune checkpoint inhibitors,ICPI)在国内外临床试验和应用中的逐步推广,越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1(programmed death-1,PD-1)及其配体(PD-1 ligand,PD-L1)免疫检查点抑制剂已被美国食品药品管理局(FDA)批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应,皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。 相似文献
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免疫检查点抑制剂能够重启并维持肿瘤-免疫循环,使抗肿瘤免疫反应正常化。目前,以抗PD-1/PD-L1单抗为代表的免疫检查点抑制剂已显著改善多种恶性肿瘤患者的预后,是免疫治疗的新里程碑。然而,单独使用抗PD-1/PD-L1单抗有效率低,与手术、化疗、放疗和靶向治疗等传统治疗手段的联合应用展现出巨大潜力,且新的免疫检查点抑制剂单药或联合使用也在研究中,从而进入后抗PD-1/PD-L1单抗时代。然而,联合方式和生物标志物的筛选仍然是关注的焦点。本文就免疫检查点抑制剂治疗现状作简要综述并对后抗PD-1/PD-L1单抗时代进行展望。 相似文献
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研究外周血生物标志物对接受PD-1/PD-L1抑制剂治疗的肺癌患者疗效的预测及指导意义。方法 收集接受PD-1/PD-L1抑制剂治疗的200例肺癌患者的资料,包括临床指标、外周血指标、疗效指标及生存指标等。结果 无肝转移、免疫联合化疗、NLR≤2.81、LDH≤202.5 u/L患者的疾病控制率(DCR)更高(P<0.05)。NLR联合LDH预测DCR的AUC值为0.698(P<0.05)。单因素分析示无肝转移、一线免疫治疗、免疫联合化疗、LDH≤202.5 u/L均与PFS有关(P<0.05)。多因素分析示无肝转移、LDH≤202.5 u/L患者的PFS更长(P<0.05)。探索性分析示两周期免疫治疗后NLR、LDH的明显下降提示免疫治疗的有效性(P<0.05)。结论 NLR≤2.81、LDH≤202.5 u/L、无肝转移、免疫联合化疗与免疫治疗疗效呈正相关,且无肝转移、LDH≤202.5 u/L是接受免疫治疗患者的独立预后因素。另外,外周血NLR、LDH的变化与PD-1/PD-L1抑制剂的疗效相关。 相似文献
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免疫治疗的发展使恶性黑色素瘤的患者总体存活率显著改善,特别是免疫检查点抑制剂(immune checkpoint inhibitor, ICIs)的出现推动了黑色素瘤免疫治疗的发展。ICIs主要针对细胞程序性死亡受体-1(programmed cell death receptor-1,PD-1)、程序性死亡配体-1(programmed death-ligand 1,PD-L1)以及细胞毒性T淋巴细胞相关蛋白-4(cytotoxic T-lymphocyte antigen-4,CTLA-4)。随着ICIs在临床上的大规模应用,越来越多的不良反应也逐渐显现,本篇主要概述PD-1单抗或PD-L1单抗在治疗中出现的不良反应类型及特点。 相似文献
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头颈鳞癌(Head and neck squamous cell carcinoma,HNSCC)患者被诊断时多为晚期,传统方案治疗后复发率约为60%、转移率约为30%。而复发/转移性头颈鳞癌(Recurrent/metastasis HNSCC,R/M HNSCC)患者的治疗手段有限,长期生存率有待提高。免疫检查点抑制剂的出现有效的提高了这些患者的总生存期,为HNSCC患者带来了希望。本文总结了近年来程序性死亡蛋白1(PD-1)、程序性死亡蛋白1配体(PD-L1)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)抑制剂及其组合疗法在头颈鳞癌中的研究进展,希望为临床医师提供新的治疗方案。 相似文献
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Xinbing Sui Junhong Ma Weidong Han Xian Wang Yong Fang Da Li Hongming Pan Li Zhang 《Oncotarget》2015,6(23):19393-19404
The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer. 相似文献
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胃癌是最为常见的恶性肿瘤之一,在中国其发病率和死亡率均较高,大多数胃癌初诊即已为晚期,预后较差,目前治疗现状仍不理想。免疫逃逸是肿瘤发生发展的一主要机制,细胞程序性死亡受体-1(programmed death-1,PD-1)及细胞程序性死亡配体(programmed death-ligand 1,PD-L1)是导致免疫逃逸的重要分子,PD-1与PD-L1结合是肿瘤细胞免疫逃逸的重要发病机制之一,特异性阻断二者结合,可达到杀灭肿瘤细胞的目的。PD-1/PD-L1抑制剂可明显改善晚期胃癌患者预后,并且PD-1/PD-L1抑制剂联合化疗、靶向治疗、放疗等可进一步提高疗效。本文就PD-1/PD-L1抑制剂联合治疗在晚期胃癌中的治疗进展进行综述。 相似文献
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B.L. King-Kallimanis B. Kanapuru G.M. Blumenthal M.R. Theoret P.G. Kluetz 《Seminars in oncology》2018,45(4):201-209
Background
Older adults with lung cancer often have comorbidities that may increase risk of symptomatic adverse events (AEs) and physical function decline. The objective of this study was to examine age-related differences in patient-reported symptoms and functional domains in patients with advanced lung cancer receiving immunotherapy drugs.Methods
Three randomized controlled trials of anti-programmed death receptor-1/programmed death-ligand 1 therapy in patients with advanced non–small cell lung cancer that included patient-reported outcomes (PROs) were identified. Baseline PRO data were pooled for treatment arms from 2 trials that included the same PRO tools. Age-related differences in baseline mean scores for each of the health-related quality of life functional and symptom scales were assessed for patients ≥70 years and <70 years. Mean change from Baseline at 3 months was also calculated and plotted for each age group. The adequacy of PRO assessments was assessed by comparing clinician-reported AE data in the 3 trials to the item content of the PRO tools included.Results
Across the 3 trials, 75 of patients were under 70 and 26% patients were 70 and older. Comparing baseline scores in the 2 trials with the same PRO tool, older adults reported small differences including lower physical functioning, less pain, insomnia and financial difficulties, and higher social functioning than younger patients at baseline. No large differences in the distributions of mean change from baseline in function or symptom were identified. Several common clinician-reported symptomatic AEs were not assessed by the PRO strategy employed in the 3 trials. Three clinician-reported symptomatic AEs (rash, fever, and pruritus) that were commonly reported in the safety data (9%–19%) were not assessed using the PRO tools employed.Conclusion
While several small differences were seen, there did not appear to be large differences at baseline or in the distributions of change from baseline in PRO functional domains between younger and older patients with lung cancer undergoing anti-programmed death receptor -1/programmed death-ligand 1 therapy. Relevant symptomatic side effects were not assessed by PRO measures in these trials, and this is a limitation of current PRO assessment strategies. 相似文献19.
Background
Immune-related adverse events (irAEs) are commonly encountered, when using programmed death-1/programmed death-ligand-1 (anti-PD-1/PD-L1) therapy and are often managed with corticosteroids. The effect of irAEs, particularly when steroids are required, on patient survival is not well established.Methods
In this retrospective analysis, data for 157 patients with various tumor types treated with anti-PD-1/PD-L1 therapy were obtained. Kaplan–Meier and Cox regression analyses were used to assess the effect of irAEs and corticosteroids on progression-free survival (PFS).Results
A total of 45 irAEs were recorded for 157 patients. Twenty-one patients received systemic corticosteroids. Patients who developed irAEs, as well as those who received systemic corticosteroids, had improved PFS by Kaplan–Meier estimate. Multivariate Cox regression showed that irAEs were associated with improved PFS (hazard ratio of 0.33, P <0.001) which persisted even with use of systemic corticosteroids (hazard ratio of 0.38, P?=?0.03).Conclusions
irAEs are associated with improved PFS in patients receiving anti-PD-1/PD-L1 therapy. This association does not appear to be altered by the use of systemic corticosteroids. 相似文献20.
作为一种新疗法,免疫检查点抑制剂(immune checkpoint inhibitor,ICI)为肿瘤的治疗带来了巨大革新.在消化道肿瘤中,少部分患者对ICI有显著的临床获益,但大部分患者仍无法获益.如何找到预测疗效的分子标志物,精准定位治疗敏感人群是消化道肿瘤免疫治疗的研究热点.本综述全面汇总了消化道肿瘤ICI治疗... 相似文献