The promising role of nivolumab in renal cell cancers

The therapeutic efficacy of checkpoint inhibitors across numerous tumor types has resulted in approval for neoplasms such as melanoma and lung cancer. Nivolumab is a fully humanized IgG4 antibody that inhibits immune checkpoint between programmed death 1 (PD-1) on T cells and PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2) on immune and cancer cells. Motzer and Colleagues published the findings of Nivolumab versus everolimus in advanced kidney cancer in the November issue of the New England Journal of Medicine. This trial showed that nivolumab resulted in better median overall survival of 25 months compared to everolimus at 19.6 months, with a hazard ratio for death at 0.73, meeting pre-specified criterion for superiority in favor of nivolumab. These findings mark the defining beneficial role of immune checkpoint inhibitor therapy in metastatic kidney cancer.     

结直肠癌免疫检查点治疗的研究进展

目前免疫治疗正在非小细胞肺癌、黑色素瘤、膀胱癌等各个瘤种中如火如荼地开展,其治疗方法也多种多样,包括肿瘤疫苗治疗、过继性T细胞疗法、免疫检查点抑制剂治疗等,但目前结直肠癌免疫治疗主要集中于免疫检查点抑制剂(PD-1/PD-L1及CTLA-4抑制剂等).自从PD-1/PD-L1抑制剂在dMMR/MSI-H晚期结直肠癌患者...     

Current and future immunotherapies for thyroid cancer

Introduction: Cancer immunotherapies were approved in recent years, including immune checkpoint inhibitors. Experience with ipilimumab (CTLA-4 antagonist), nivolumab and pembrolizumab (PD-1 antagonists), and atezolizumab (PD-L1 antagonist) has shown that the impact on overall survival in cancer patients is paramount. Immune checkpoint inhibitors target the immune system and they can be applied across multiple cancers; the response rate is ranging from 20 to 40%. Many studies have shown that thyroid cancer (TC) cells produce cytokines and chemokines, inducing several tumor-promoting effects. Targeting and/or lowering cytokines and chemokines concentrations within the tumor microenvironment would produce a therapeutic benefit. In TC, increased Treg and PD-1⁺ T cell frequencies are indicative of aggressive disease and PD-L1 expression correlates with a greater risk of recurrence.

Area covered: After performing a literature search, a few pioneering studies have evaluated immunotherapy in thyroid cancer. More recently a case has been described involving anaplastic thyroid cancer treated with vemurafenib and nivolumab, with substantial regression and complete radiographic and clinical remission.

Expert commentary: The use of immune checkpoint inhibitors in aggressive TC has not yet been extensively investigated and further studies in a large number of TC patients are urgently needed.     

Targeting the PD-1/PD-L1 axis in non–small cell lung cancer

The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non–small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing. Moreover, pembrolizumab has shown a survival advantage in the first-line setting; however, nivolumab failed to show a survival benefit possibly relating to patient selection based on PD-L1 expression. Current patient selection is based on PD-L1 expression, using the relevant companion diagnostic test, where patients with strong PD-L1 expression being more likely to respond to these novel agents. Ongoing clinical research focuses on the development of PD-1 and PD-L1 inhibitor monotherapy in neoadjuvant and adjuvant NSCLC. There is also much interest in using these drugs as a therapeutic backbone for rational combinations with other treatment modalities including cytotoxic chemotherapies in the first-line NSCLC, other immunotherapies such as cytotoxic T-lymphocyte–associated protein 4 antagonists, molecularly targeted agents including EGFR and ALK inhibitors, and radiotherapy. Concurrent treatment with radiotherapy is of particular interest owing to the potential for the abscopal effect, using radiotherapy to facilitate systemic treatment.     

A Multicenter,Randomized Phase III Study Comparing Platinum Combination Chemotherapy Plus Pembrolizumab With Platinum Combination Chemotherapy Plus Nivolumab and Ipilimumab for Treatment-Naive Advanced Non–Small Cell Lung Cancer Without Driver Gene Alterations: JCOG2007 (NIPPON Study)

BackgroundFirst-line treatment of non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination chemotherapy together with an immune checkpoint inhibitor, regardless of the expression level of the programmed cell death–1 (PD-1) ligand PD-L1 on tumor cells. Moreover, such chemotherapy plus nivolumab (antibody to PD-1) and ipilimumab (antibody to cytotoxic T lymphocyte–associated protein–4) prolonged survival in advanced NSCLC patients compared with chemotherapy alone. We have now designed a randomized, controlled phase III trial (NIPPON, JCOG2007) to confirm that platinum combination chemotherapy plus nivolumab and ipilimumab is superior to such chemotherapy plus pembrolizumab (antibody to PD-1) for treatment-naive patients with advanced NSCLC.Patients and MethodsChemotherapy-naïve patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive platinum combination chemotherapy and either pembrolizumab or nivolumab plus ipilimumab. Patients with known genetic driver alterations such as those affecting EGFR or ALK are excluded. Enrollment of 422 patients over 3 years at 55 oncology facilities throughout Japan is planned. The primary endpoint is overall survival. In addition, as ancillary research, metagenomic analysis of the gut microbiota will be performed with fecal samples collected before treatment onset, and the results will be examined for their association to therapeutic effect and adverse events.ConclusionIf the primary endpoint is met, platinum combination chemotherapy together with nivolumab plus ipilimumab will be established as a new, more effective standard treatment for advanced NSCLC.     

免疫检查点抑制剂在前列腺癌治疗中的研究进展北大核心

肿瘤诱导的免疫抑制状态在包括前列腺癌(PC)在内的癌症的发病机制中起着至关重要的作用。细胞毒T淋巴细胞相关抗原4(CTLA-4)和程序性死亡受体-1(PD-1)及其配体PD-L1是近年来研究比较透彻的免疫检查点分子。通过阻断免疫检查点(主要针对CTLA-4和PD-1/PD-L1通路)来增强细胞介导的抗肿瘤免疫成为研究热点。本文主要综述了免疫检查点抑制剂及其用于晚期前列腺癌的理论基础和前列腺癌治疗中的进展。     

Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy

Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. The main problem with checkpoint blockers is that only a fraction of patients respond to the therapy. Insufficient immune activation is considered as one of the main reason for low response rates and combination of checkpoint blockers has been proposed to increase the response rates. The combination of checkpoint blockers was successful in melanoma but had significant adverse events. A combination that is selected based on the mechanistic differences between checkpoints and the differences in expression of checkpoints and their ligands in the tumor microenvironment could have a synergistic effect in a given cancer subtype and also have a manageable safety profile. This review aims to help in design of optimal checkpoint blocker combinations by discussing the mechanistic details and outlining the subtle differences between major checkpoints targeted for cancer immunotherapy.     

PD-1 pathway inhibitors: The next generation of immunotherapy for advanced melanoma

Checkpoint inhibitors are revolutionizing treatment options and expectations for patients with melanoma. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), was the first approved checkpoint inhibitor. Emerging long-term data indicate that approximately 20% of ipilimumab-treated patients achieve long-term survival. The first programmed death 1 (PD-1) inhibitor, pembrolizumab, was recently approved by the United States Food and Drug Administration for the treatment of melanoma; nivolumab was previously approved in Japan. PD-1 inhibitors are also poised to become standard of care treatment for other cancers, including non-small cell lung cancer, renal cell carcinoma and Hodgkin''s lymphoma. Immunotherapy using checkpoint inhibition is a different treatment approach to chemotherapy and targeted agents: instead of directly acting on the tumor to induce tumor cell death, checkpoint inhibitors enhance or de novo stimulate antitumor immune responses to eliminate cancer cells. Initial data suggest that objective anti-tumor response rates may be higher with anti-PD-1 agents compared with ipilimumab and the safety profile may be more tolerable. This review explores the development and next steps for PD-1 pathway inhibitors, including discussion of their novel mechanism of action and clinical data to-date, with a focus on melanoma.     

Cutaneous Adverse Events Associated with Immune Checkpoint Inhibitors: A Review Article

Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients.     

Immune checkpoint inhibitors in advanced renal cell carcinoma: experience to date and future directions

In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. Despite these advances, patient outcomes remain suboptimal, underscoring the need for therapeutic interventions with novel mechanisms of action. The advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for several solid malignancies. Specifically, drugs targeting the programmed death 1 (PD-1) and cytotoxic T-lymphocyte associated antigen (CTLA-4) pathways have demonstrated considerable clinical efficacy and gained regulatory approval as single-agent or combination therapy for the treatment of patients with metastatic melanoma, non-small cell lung cancer, aRCC, advanced squamous cell carcinoma of the head and neck, urothelial cancer and Hodgkin lymphoma. In aRCC, the PD-1 inhibitor nivolumab was approved in both the United States and Europe for the treatment of patients who have received prior therapy, based on improved overall survival compared with the mTOR inhibitor everolimus. Other checkpoint inhibitors, including the CTLA-4 inhibitor ipilimumab in combination with several agents, and the PD-L1 inhibitor atezolizumab, are in various stages of clinical development in patients with aRCC. In this review, current evidence related to the clinical use of checkpoint inhibitors for the treatment of patients with aRCC is discussed, including information on the frequency and management of unconventional responses and the management of immune-related adverse events. In addition, perspectives on the future use of checkpoint inhibitors are discussed, including the potential value of treatment beyond progression, the potential use in earlier lines of care or in combination with other agents, and the identification of biomarkers to guide patient selection and enable individualization of therapy.     

免疫检查点抑制剂在结直肠癌中的研究进展CSCD

免疫治疗是当前实体肿瘤治疗研究的新方向,而在免疫系统中发挥负性调节分子的免疫检查点在限制抗肿瘤免疫反应中起着关键作用。针对PD-1及PD-L1、CTLA-4的免疫检查点抑制剂已被开发为抗肿瘤药物进行临床研究,dMMR/MSI-H型结直肠癌对免疫检查点抑制剂具有客观反应。本文基于结直肠癌免疫分型,对免疫检查点抑制剂在结直肠癌中的治疗方案进行综述。     

Next steps in immuno-oncology: enhancing antitumor effects through appropriate patient selection and rationally designed combination strategies

BackgroundCancers escape immune surveillance via distinct mechanisms that involve central (negative selection within the thymus) or peripheral (lack of costimulation, receipt of death/anergic signals by tumor, immunoregulatory cell populations) immune tolerance. During the 1990s, moderate clinical benefit was seen using several cytokine therapies for a limited number of cancers. Over the past 20 years, extensive research has been performed to understand the role of various components of peripheral immune tolerance, with the co-inhibitory immune checkpoint molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1) being the most well-characterized at preclinical and clinical levels.Patients and methodsWe used PubMed and Google Scholar searches to identify key articles published reporting preclinical and clinical studies investigating CTLA-4 and PD-1/PD-L1, frequently cited review articles, and clinical studies of CTLA-4 and PD-1/PD-L1 pathway inhibitors, including combination therapy strategies. We also searched recent oncology congress presentations and clinicaltrials.gov to cover the most up-to-date clinical trial data and ongoing clinical trials of immune checkpoint inhibitor (ICI) combinations.ResultsInhibiting CTLA-4 and PD-1 using monoclonal antibody therapies administered as single agents has been associated with clinical benefit in distinct patient subgroups across several malignancies. Concurrent blockade of CTLA-4 and components of the PD-1/PD-L1 system using various schedules has shown synergy and even higher incidence of durable antitumor responses at the expense of increased rates of immune-mediated adverse events, which can be life-threatening, but are rarely fatal and are reversible in most cases using established treatment guidelines.ConclusionsDual immune checkpoint blockade has demonstrated promising clinical benefit in numerous solid tumor types. This example of concurrent modulation of multiple components of the immune system is currently being investigated in other cancers using various immunomodulatory strategies.     

复发转移性头颈鳞状细胞癌免疫治疗现状和探索

目的 世界范围内,头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)发病率在恶性肿瘤中居第7位,复发转移性(recurrent or metastatic,R/M) HNSCC生活质量下降,治疗方法少,预后差.近年来,以免疫检查点抑制剂为代表的免疫治疗取得突破性进展,成为黑色素瘤、肺癌等多种肿瘤有效的治疗选择.本研究对R/M HNSCC免疫治疗的现状和进展作一综述.方法 以“头颈鳞癌,免疫治疗,免疫检查点抑制剂,过继T细胞治疗,肿瘤疫苗”等为关键词,应用PubMed和CNKI期刊全文数据库检索系统以及ClinicalTrials.gov网站,检索2001-01-2017-01的相关文献及注册临床研究,共检索到英文文献138篇,中文文献84篇.纳入标准:(1)R/M HNSCC;(2)免疫治疗现状及进展;(3)免疫治疗相关临床研究.共纳入38篇文献进行分析.结果 R/M HNSCC中免疫治疗研究广泛开展并逐渐深入,尤其是免疫检查点抑制剂.程序性细胞死亡1(programmed cell death-1,PDq)抑制剂(Pembrolizumab和Nivolumab)显示出明显疗效,因此被食品药品管理局(food and drug administration,FDA)批准用于R/M HNSCC的治疗.尽管其他免疫检查点抑制剂如程序性死亡配体1(programmed death ligand-1,PD-L1)抑制剂(Durvalumab和Avelumab)和细胞毒T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)抑制剂(Ipilimumab和Tremelimumab)尚无Ⅲ期临床研究结果发表来证明其确切疗效,但有一系列临床研究正在进行中.过继T细胞治疗和肿瘤疫苗的免疫治疗模式也在探索中.此外,在R/M HNSCC免疫治疗中根据生物标志物筛选有效患者,联合治疗提高疗效以及不良反应的监测及治疗等方面也被关注.结论 R/M HNSCC中免疫治疗有良好前景,但也存在许多挑战,如何筛选免疫治疗最有效的人群、探索免疫治疗模式及提高疗效仍是未来研究重点.     

Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond

Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC.     

Health-related quality of life results from the phase III CheckMate 067 study

BackgroundNivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL). Here we report analyses of HRQoL for patients with advanced melanoma in clinical trial CheckMate 067.Patients and methodsHRQoL was assessed at weeks 1 and 5 per 6-week cycle for the first 6 months, once every 6 weeks thereafter, and at two follow-up visits using the European Organization for Research and Treatment of Care Core Quality of Life Questionnaire and the EuroQoL Five Dimensions Questionnaire. In addition to the randomised population, patient subgroups, including BRAF mutation status, partial or complete response, treatment-related AEs of grade 3/4, and those who discontinued due to any reason and due to an AE, were investigated.ResultsNivolumab and ipilimumab combination and nivolumab alone both maintained HRQoL, and no clinically meaningful deterioration was observed over time compared with ipilimumab. In addition, similar results were observed across patient subgroups, and no clinically meaningful changes in HRQoL were observed during follow-up visits for patients who discontinued due to any cause.ConclusionThese results further support the clinical benefit of nivolumab monotherapy and nivolumab and ipilimumab combination therapy in patients with advanced melanoma. The finding that the difference in grade 3/4 AEs between the arms did not translate into clinically meaningful differences in the reported HRQoL may be relevant in the clinical setting.Study numberNCT01844505.     

肺鳞癌的免疫治疗进展

近几年来,肺鳞癌在化疗及靶向治疗上的进展不够显著,但免疫治疗却在肺鳞癌的治疗上取得了突破性的进展。免疫治疗通过免疫系统来清除肿瘤细胞,主要分为免疫检查点抑制剂及治疗性疫苗。免疫检查点抑制剂,包括抗细胞毒性T淋巴细胞抗原4（cytotoxic T-lymphocyte associated antigen 4, CTLA-4）抗体与抗程序性死亡受体-1（programmed death receptor 1, PD-1）抗体等多种药物已进行了肺鳞癌的II期、III期临床试验,并取得了一定成果。免疫治疗将成为肺鳞癌治疗的一种重要手段。     

Biomarkers of response to PD-1 pathway blockade

The binding of T cell immune checkpoint proteins programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to their ligands allows immune evasion by tumours. The development of therapeutic antibodies, termed checkpoint inhibitors, that bind these molecules or their ligands, has provided a means to release this brake on the host anti-tumour immune response. However, these drugs are costly, are associated with potentially severe side effects, and only benefit a small subset of patients. It is therefore important to identify biomarkers that discriminate between responders and non-responders. This review discusses the determinants for a successful response to antibodies that bind PD-1 or its ligand PD-L1, dividing them into markers found in the tumour biopsy and those in non-tumour samples. It provides an update on the established predictive biomarkers (tumour PD-L1 expression, tumour mismatch repair deficiency and tumour mutational burden) and assesses the evidence for new potential biomarkers.Subject terms: Tumour biomarkers, Cancer immunotherapy, Predictive markers     

免疫检查点抑制剂治疗相关静脉血栓栓塞症的研究进展

近年来,静脉血栓栓塞症(venous thromboembolism, VTE)已成为仅次于恶性肿瘤本身的第二位死亡原因。在精准治疗时代,既往标准癌症治疗手段已证实与VTE形成密切相关,如手术、化疗以及抗血管生成靶向治疗等。当代基于程序性死亡受体及其配体(programmed cell death 1 or its ligand, PD-1/PD-L1)或细胞毒性T淋巴细胞抗原4(cytotoxic T-lymphocyte antigen 4,CTLA4)为治疗靶点的免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)的应用日趋成为常态并已成为指南推荐。然而,由ICIs诱导的各种非靶向自身免疫表现即免疫相关不良事件(immune-related adverse events, irAEs)不容忽视,其诱导的全身炎症对止血系统的影响迄今尚未得到适当研究。因此,临床医生非常有必要加强对ICIs相关VTE不良事件的认识。本文就ICIs相关VTE的发生率、危险因素、发病机制及临床管理原则等方面进行综述,以期为临床实践中免疫治疗相关静脉血栓的一级预防及精准治...     

Management of toxicities of immune checkpoint inhibitors

Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided.     

PD-1/PD-L1在急性髓系白血病中的研究进展和临床应用

急性髓系白血病（AML）的治疗是一个世界性范围的难题,尽管化学治疗和异基因造血干细胞移植（allo-HSCT）能够一定程度的提高患者的缓解率和治愈率,但是治疗相关并发症和复发仍严重影响治疗的效果。免疫检查点是近年来恶性肿瘤研究的热点之一,这种免疫学机制和临床疗法可能给予治疗AML新的希望。免疫疗法与传统化疗的不同之处在于,它作用于免疫细胞,而不是癌细胞本身。针对T细胞免疫检查点的单克隆抗体CTLA-4、PD-1和PD-L1以及免疫微环境细胞上的PD-L1现已被批准用于多种实体肿瘤和血液系统恶性肿瘤的临床治疗。本文综述了PD-1与PD-L1结合后在AML上造成的免疫逃逸机制及免疫检查点抑制剂运用于治疗AML中的临床试验结果。