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免疫检查点抑制剂(ICIs)使多种晚期恶性肿瘤的治疗模式开启了新变革.尽管免疫检查点抑制剂相关心脏毒性较为罕见,但致死性极高.以往研究中免疫检查点抑制剂心脏毒性的发生率被低估.本综述聚焦于目前免疫检查点抑制剂心脏毒性方面的研究进展,包括流行病学、评估、诊断、治疗和预后等.接受ICIs治疗者的最佳肿瘤心脏病管理模式仍面临... 相似文献
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免疫检查点抑制剂通过阻断T淋巴细胞负性调控信号以达到增强T淋巴细胞抗肿瘤效应的同时,也可能造成免疫耐受失衡或正常免疫亢进从而导致免疫性肝炎。本文主要通过对免疫检查点抑制剂的治疗机制,导致肝损伤的不良反应机制、危险因素以及发生率等方面进行回顾分析,并且对免疫检查点抑制剂导致肝损伤的治疗方法进行初步归纳。认为免疫检查点抑制剂在促进抗肿瘤免疫的同时,由于作用机制的非肿瘤组织靶点特异性,可能造成非同质化的免疫相关的肝损伤,治疗上以恢复免疫稳态为主。因此,免疫检查点抑制剂应用患者的管理往往需要在治疗窗、毒性和特定损伤治疗之间取得平衡,并开展多学科协作。 相似文献
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《中华内科杂志》2021,(11)
近年来, 免疫治疗在肿瘤的治疗中发挥着越来越重要的作用, 尤其是免疫检查点抑制剂, 为晚期肿瘤患者生存期的延长带来了巨大获益。免疫检查点抑制剂是以免疫细胞或肿瘤细胞表面的具有抑制免疫细胞功能的受体或配体为靶点而研发的一些单克隆抗体类药物, 其通过阻断表达于肿瘤细胞与免疫细胞间的免疫检查点间的相互作用, 阻断肿瘤细胞对免疫细胞的抑制作用。程序性死亡受体1(PD-1)和程序性死亡受体-配体1(PD-L1)单克隆抗体是目前研究最为广泛的两种免疫检查点抑制剂。本文主要从PD-1/PD-L1通路的生理作用、肿瘤免疫逃逸、PD-1/PD-L1单抗抗肿瘤作用、耐药及免疫相关不良反应发生机制等几个角度出发, 对PD-1/PD-L1单克隆抗体的抗肿瘤机制及新型肿瘤免疫治疗靶点进行全面综述。 相似文献
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《世界华人消化杂志》2017,(19)
结直肠癌(colorectal cancer,CRC)是消化系最常见的恶性肿瘤之一,在我国,其发病率及死亡率处于逐年上升趋势,且总体预后相对较差.近年来,免疫治疗的基础和临床研究都获得了快速发展,已成为肿瘤研究的热点.其中,免疫检查点抑制剂已经被批准用于包括CRC在内的多种实体肿瘤的临床治疗.本文将重点阐述免疫检查点的作用、机制和免疫检查点抑制剂在CRC中应用的最新进展,以及影响其抗肿瘤疗效的因素.已经完成和正在进行的临床试验肯定了免疫检查点抑制剂在CRC的治疗中的潜力,尽管部分患者仍对免疫检查点治疗无应答.因此,探究免疫检查点抑制剂治疗CRC患者的敏感因素,对实现个体化精准治疗至关重要.未来,免疫检查点抑制剂有望和其他多种治疗方法相联合,提高患者反应率,延长患者的生存期. 相似文献
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免疫治疗是近年来肿瘤治疗领域的热点,在各个瘤种中均进行了广泛的探索性研究。本文对食管癌免疫治疗的相关研究进展进行综述,全面分析免疫检查点抑制剂在食管癌中的治疗效果,同时寻找能够预测治疗效果的分子生物学标记。以食管癌、免疫治疗、免疫检查点抑制剂为关键词进行文献检索,共检索中文文献6篇,英文文献27篇,排除10篇,最终对23篇文献进行分析。在NCCN治疗指南中,错配修复蛋白缺失突变(dMMR)和微卫星高度不稳定(MSI-H)的患者应用PD-1单抗是晚期食管癌的标准二线治疗。无论是免疫单药、免疫联合治疗在食管癌一线、二线以及新辅助治疗中都进行了尝试。免疫治疗在食管癌治疗中显示出一定的生存获益,筛选能够预测免疫检查点抑制剂疗效的生物学标记物是提高疗效的关键。 相似文献
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Immunotherapy with immune checkpoint inhibitors has been shown to be beneficial for cancers originating from various organs. In May 2020, combination therapy with anti-programmed death-ligand 1 antibody atezolizumab and anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was approved as a novel first-line systemic therapy for hepatocellular carcinoma (HCC). The number of patients with HCC not caused by hepatitis virus infection (non-viral HCC), including non-alcoholic steatohepatitis (NASH)-related HCC, has been increasing in recent years. Recently, Pfister and colleagues reported that immune checkpoint inhibitors may exhibit limited efficacy against NASH-related HCC, based on basic research and clinical data. This review will discuss the mechanism of impaired tumor immune surveillance in NASH and analyze the results of previously published clinical trials of immune checkpoint inhibitors to investigate whether patients with non-viral HCC are less likely to benefit from immunotherapy with immune checkpoint inhibitors. Furthermore, we also discuss the possibility of enhancing the therapeutic effect of immune checkpoint inhibitors for NASH-related HCC by combining anti-VEGF agents. 相似文献
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Background:Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in non-small cell lung cancer (NSCLC) patients. However, we still have no clear ideas of the factors which could affect the efficacy of immune checkpoint inhibitors. Cancer, essentially, is a disease related to genes mutation. Therefore, we conducted a systematic review and meta-analysis to compare efficacy of immune checkpoint inhibitors for NSCLC patients with different genes mutation.Methods:PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched for all clinical trials in NSCLC until December 16, 2019. The hazard ratio (HR) and 95% confidence intervals (CIs) of OS or progression-free survival (PFS) were used.Results:A total of 4453 patients from 7 randomized controlled trials (RCTs) were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.67; 95% CI, 0.60–0.67) in NSCLC patients having epidermal growth factor receptor (EGFR) wild-type versus chemotherapy. Meanwhile, they prolonged the OS (HR, 0.61; 95% CI, 0.39–0.94) in NSCLC patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. No matter PD-L1 tumor proportion scores were >1% or <1%, immune checkpoint inhibitors were more effective than chemotherapy (HR, 0.64; 95% CI, 0.55–0.75).Conclusion:Immune checkpoint inhibitors are more efficacious than chemotherapy in NSCLC patients with EGFR wild-type, KRAS mutation, and any PD-L1 tumor proportion scores. 相似文献
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免疫检查点抑制剂(ICI)通过阻断肿瘤细胞的免疫逃逸,调动自身免疫反应达到治疗肿瘤的目的.ICI可导致多种免疫相关不良反应,其中心脏毒性是少见但致命的不良反应.随着ICI在临床中使用的增加,其导致的心脏毒性逐渐引起更多关注.本文就ICI相关心脏毒性临床表现、机制、诊治及预后进行综述. 相似文献
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Marko Jakopovic Lela Bitar Fran Seiwerth Ante Marusic Kristina Krpina Miroslav Samarzija 《Journal of thoracic disease》2020,12(12):7635
Thymic epithelial tumors (TETs) are rare thymic neoplasms. There are approximately 1.5 cases per million TETs per year. They are the most common anterior mediastinal tumors in adults. Due to limited activity of available treatment options novel strategies and treatment options are needed and treatment with immune checkpoint inhibitors is an attractive option. Thymic epithelial tumors have one of the lowest tumor mutational burden among all cancer in adults, but high expression of PD-L1 on tumor cells and abundant CD8+ lymphocytes provide a strong rational for implementing immune checkpoint inhibitors (ICIs) which target PD-1/PD-L1 pathway in the treatment of TETs. Few small early stage clinical trials were published so far evaluating efficacy of pembrolizumab and avelumab in thymoma and thymic carcinoma patients. Al trials showed reasonable response rates and progression-free survival. Higher PD-L1 expression was predictor of response in all trials. However, increased incidence of immune-related adverse events was seen in TET patients treated with immune checkpoint inhibitors compared to patients with other cancers. At the moment, ICIs are not standard of care for patients with TET and larger trials are needed to establish the right role of ICIs regarding efficacy and safety of these agents. 相似文献
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Hepatocellular carcinoma (HCC) is one of the most common cancers with a high recurrence rate. Currently, tyrosine kinase inhibitors (TKIs) are the first‐line treatment for cases refractory to conventional therapies. However, the acquisition of somatic mutations can result in TKI resistance. Clinical evidence suggests that acquired immunity contributes to the suppression of tumor recurrence, indicating the potential of induced antitumor immune reaction for the treatment of HCC. Recently, immune checkpoint inhibitors have become available for the treatment of malignancies. They are effective regardless of the response to prior therapies and a durable effect can be expected, which should be attributed to an adaptive immunity to HCC components. The results of phase I/II trials of nivolumab, an anti‐programmed cell death‐1 antibody, showed that 20% of patients showed objective response and that nivolumab was effective regardless of prior sorafenib treatment and viral status. Nivolumab received expedited Food and Drug Administration approval in 2017 for the treatment of advanced HCC after failure or intolerance to sorafenib. However, the majority of the patients remain refractory, likely due to the solid immune suppressive status, which involves many stromal cells, humoral mediators, and suppressive checkpoint molecules. Therefore, current clinical trials are focusing on how immunosuppressive conditions in HCC might be overcome using immune checkpoint inhibitors in combination with different types of immune checkpoint blockades, TKIs, and other conventional treatments. The development of immune checkpoint inhibitors is rapidly progressing and these inhibitors are likely to be key agents for HCC treatment in the near feature. 相似文献
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《Best Practice & Research: Clinical Haematology》2018,31(3):299-305
The idea that the immune system could be co-opted to treat cancer is not new; it has existed for centuries. However, what is new is the advancement of our understanding of how the immune system is regulated and how a tumor evolves to evade an immune response. This knowledge, combined with modern technologies to manipulate the immune system, both pharmacologically and genetically, has led to the realization of immuno-oncology as a new frontier in cancer therapeutics. This review will focus on pharmacologic immunotherapies in aggressive B cell lymphomas: checkpoint inhibition and bispecific antibodies. The success of checkpoint inhibitors in this heterogenous collection of diseases has largely been limited to those that genetic aberrations involving genes for checkpoint ligands, whereas bispecific antibodies appear to be more broadly efficacious but responses are short-lived. Investigation into the tumor microenvironment for each of the aggressive B cell lymphoma histologies, and interrogation of mechanisms of resistance as well as predictors of response to these immunotherapy approaches, will undoubtedly identify rational combinations as well as new therapeutic targets such that outcomes can be improved across these diseases. 相似文献
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Daniela Cornelia Laz?r Mihaela Flavia Avram Ioan Romo?an M?rioara Cornianu Sorina T?ban Adrian Goldi? 《World journal of gastroenterology : WJG》2018,24(32):3583-3616
Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with differentclinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects. 相似文献