肺癌免疫检查点抑制剂治疗的不良反应及其防治

肺癌免疫检查点抑制剂(主要为抗PD-1或PD-L1类药物)可显著提升晚期肺癌患者的5年生存率,目前在晚期肺癌一线及二线治疗中占据重要地位,未来将成为肺癌治疗的主要措施之一,而呼吸领域的临床医生对其不良反应还缺乏足够的认识.本文简要介绍肺癌免疫检查点抑制剂治疗的不良反应及其防治.     

肺癌免疫检查点抑制剂治疗:从临床研究到临床实践

肺癌是全球范围内发生率和死亡率最高的恶性肿瘤.近年来,免疫检查点抑制剂在非小细胞肺癌和小细胞肺癌的治疗中均有突破,改变了肺癌治疗策略的格局,也改善了患者的生存结局.本文对免疫检查点抑制剂在肺癌治疗中的使用时机、疗效、安全性和适用人群进行探讨.     

免疫检查点抑制剂联合放化疗治疗非小细胞肺癌的疗效预测标志物研究进展

肺癌已成为我国死亡率最高的恶性肿瘤,其中非小细胞肺癌占肺癌的85%~90%,且发病率呈逐年增高趋势[1]。大多数非小细胞肺癌诊断时已出现远处转移,无法手术治疗。放疗、化疗、靶向治疗和抗血管生成治疗是晚期非小细胞肺癌患者的主要治疗方法。而肿瘤免疫治疗在肺癌中的应用既往一直未有突破性的进展,其治疗策略主要集中于直接提高抗肿瘤主动免疫(如过继性细胞免疫治疗)[2]。随着对肿瘤免疫微环境研究的深入,免疫检查点(immune checkpoint)在肿瘤免疫逃逸中的作用逐渐被重视,而针对免疫检查点的抑制剂(immune checkpoint inhibitors,ICIs)开始进入临床应用,并显示出一定的治疗效果。其中,程序性死亡受体-1/配体-L1(programmed cell death 1,PD-1/Programmed cell death 1 ligand 1,PD-L1)抑制剂已经获批应用于晚期非小细胞肺癌的治疗。     

老年晚期非小细胞肺癌患者免疫检查点抑制剂研究进展

肺癌是最常见的老年恶性肿瘤之一,以免疫检查点抑制剂为代表的免疫治疗利用机体免疫系统达到有效的抗肿瘤效应。在晚期非小细胞肺癌(NSCLC)患者中,免疫检查点抑制剂单药治疗及联合治疗已成为重要的治疗手段,现对免疫检查点抑制剂类药物在老年晚期NSCLC患者中应用的效果、不良反应、超进展情况进行综述,为老年NSCLC免疫治疗策...     

免疫检查点抑制剂心脏毒性的临床热点与争议

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...     

非小细胞肺癌免疫检查点抑制剂相关性肺炎的研究进展

近年来, 肺癌的发病率逐年上升, 手术及放化疗作为肺癌的传统治疗手段, 临床效果较为有限, 免疫检查点抑制剂改变了晚期非小细胞肺癌患者的治疗格局。然而, 免疫检查点抑制剂也会引发与免疫相关的不良事件, 免疫检查点抑制剂相关性肺炎(CIP)是其中较为严重的不良反应, 并且在很大程度上影响了癌症患者的治疗和预后。因此, 进一步认识CIP就显得至关重要, 本文旨在对CIP的发病机制、危险因素、临床表现、分型、诊断及治疗进行系统性的综述。     

免疫检查点抑制剂在结直肠癌中的应用以及未来发展方向

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.     

免疫治疗——开启肺癌治疗的新时代

以免疫检查点抑制剂为代表的免疫治疗已成为晚期非小细胞肺癌二线标准治疗方案,其一线治疗的适应证也在逐步获批,肺癌免疫治疗正向着早期新辅助治疗方向推进.在免疫单药治疗取得突破性进展后,免疫联合放疗、化疗及双免疫治疗使患者的疗效进一步提高,强强联合是肺癌治疗的大势所趋.免疫治疗在非小细胞肺癌领域疗效显著,并向小细胞肺癌领域扩展,使越来越多的患者受益.肺癌免疫治疗同时面临诸多挑战,如何筛选肺癌免疫治疗的获益人群,如何优化免疫治疗的方案,如何评估免疫治疗的疗效,如何克服免疫治疗的耐药,以及如何监测管理免疫相关不良反应等一系列问题亟待解决.我国自主研发的免疫检查点抑制剂也在临床研究或审批中,肺癌免疫治疗将会给我国肺癌患者带来更多的福音.     

免疫检查点抑制剂在肺癌治疗中的应用研究进展

免疫检查点抑制剂是一类针对细胞程序性死亡受体1(PD-1)、程序性死亡配体1(PD-L1)以及毒性T淋巴细胞抗原4(CTLA-4)的人源化单克隆抗体药物。在非小细胞肺癌患者的治疗方面,免疫检查点抑制剂表现出了显著且更加持久的疗效。本文就当前这类药物在肺癌治疗中的作用机制、临床研究最新进展以及相关生物标志物的预后和预测作用进行综述。     

免疫检查点抑制剂在驱动基因阳性非小细胞肺癌治疗中的研究进展

近年来, 免疫检查点抑制剂显著改善了部分肺癌患者的生存和预后。驱动基因阳性非小细胞肺癌患者免疫疗法往往效果不佳, 且常伴随免疫治疗相关不良反应, 因此争议较大。近来一些研究证明伴有驱动基因改变的肺癌患者也可受益于免疫治疗, 这可能为相关患者提供更多治疗选择, 值得进一步研究。本文对免疫检查点抑制剂在驱动基因阳性非小细胞肺癌患者治疗中的研究进展进行综述。     

Lungenkarzinom und rheumatoide Arthritis

Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data.     

结直肠癌的免疫检查点阻断治疗

结直肠癌是常见的恶性肿瘤之一,总体预后相对较差。对转移性结直肠癌患者而言,探索更有效的治疗方法显得尤为重要。免疫治疗,特别是免疫检查点抑制剂,是近几年研究的热点,在黑色素瘤、肺癌等疾病中取得了较好的疗效。本文将重点阐述抗肿瘤免疫在结直肠癌中的作用,以及各种免疫检查点抑制剂在结直肠癌中应用的最新进展。     

Immune checkpoint therapy for pancreatic cancer

Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy. However, due to small sample sizes, major results are not yet identifiable. The present article provides a clinical overview of immune checkpoint inhibition in pancreatic cancer. Pub Med, Clinical Trials.gov and American Society of Clinical Oncology's meeting abstracts were systematically searched for relevant clinical studies. Four articles, five abstracts and 25 clinical trials were identified and analyzed in detail.     

Immunotherapy for lung cancer

Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer‐related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.     

Small cell lung cancer; recent advances of its biology and therapeutic perspective

Lung cancer is historically divided into two major categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While the therapeutic efficacy of NSCLC has improved due to the development of molecular targeted therapy and immune checkpoint inhibitors (ICIs) treatment, there has been very slow progress in the therapeutic advances of SCLC. Since SCLC is a deadly disease with rapid progression and early metastasis and comprises approximately 10% of lung cancer cases, more attention should be given to the therapeutic strategy for SCLC. Most SCLC cases respond to cytotoxic drugs, cisplatin, and etoposide. The objective response rate to the standard regimen is reported to be approximately 70% that is sufficient as standard therapy. However, almost all tumors recur and become refractory to chemotherapy which is the most important problem of this deadly disease.Recently, for the first time in several decades, ICIs have changed the standard therapy for SCLC. It must be emphasized that although ICIs paved the new way for SCLC therapy, more precise and effective therapy for SCLC is desired. Unfortunately, precise molecular mechanisms of SCLC are yet to be understood. Recent elaborate studies on the cell biology of SCLC uncovered several important aspects of molecular mechanisms. Gene profiling of cancer cells can be done using modern technology like next-generation sequencing (NGS). In this minireview, we describe the advances of modern technology in SCLC research and consider future therapeutic strategies based on the molecular mechanisms of SCLC.     

Nueva inmunoterapia y cáncer de pulmón

Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response.These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%-25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results.This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents.     

Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer

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.     

Does immune checkpoint inhibitor exhibit limited efficacy against non-viral hepatocellular carcinoma?: A review of clinical trials

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.     

分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在肝细胞癌中的应用

肝细胞癌(HCC)是最常见的恶性肿瘤之一,发病隐匿,发展迅速,高复发的特点导致HCC患者长期生存面临巨大挑战。分子靶向药物与免疫抑制剂在HCC治疗中成为研究的热点,大量临床试验发现,联合治疗取得了不错的疗效。主要介绍了分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在HCC中的应用,指出当前HCC治疗的最新研究热点在于系统治疗或局部治疗相关的联合治疗。     

肠道菌群与肝癌免疫治疗的研究进展

肠道菌群对人类的健康发挥了重要作用.研究发现,肠道菌群在肿瘤的发生和肿瘤免疫治疗中也起着关键作用.目前,免疫治疗在肝癌治疗领域取得了重要进展.尽管免疫治疗可以提高肝癌患者的生存,但是目前其疗效仍不够满意.调节肠道菌群组成,特别是使有助于免疫治疗效果的菌群在肠道富集,可能会使得肝癌免疫治疗的效果得到提高.本文就肠道菌群与肝癌免疫治疗的相关研究进展进行综述.