老年肿瘤免疫检查点抑制剂临床治疗进展

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)是当今肿瘤治疗领域的革命性突破, 改变了多种肿瘤治疗模式。老年人占肿瘤现患人数及死亡人数的绝大部分, 老年肿瘤患者存在免疫衰老、自身免疫性疾病及感染性疾病发生率高、肿瘤突变负荷与年轻患者存在差异等均可能影响ICIs疗效。在大部分ICIs临床试验中, 老年肿瘤患者在受试人群中未能占据应有比例, 亚组分析及荟萃分析结果提示年龄对疗效及免疫相关不良反应的发生影响较小。临床医生可参考相关试验数据, 在体能状态较好的老年肿瘤患者中使用ICIs, 以积累更多的真实世界数据。     

Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy

Neurologic autoimmune disorders in the context of systemic cancer reflect antitumor immune responses against onconeural proteins that are autoantigens in the nervous system. These responses observe basic principles of cancer immunity and are highly pertinent to oncological practice since the introduction of immune checkpoint inhibitor cancer therapy. The patient’s autoantibody profile is consistent with the antigenic composition of the underlying malignancy. A major determinant of the pathogenic outcome is the anatomic and subcellular location of the autoantigen. IgGs targeting plasma membrane proteins (eg, muscle acetylcholine receptor -IgG in patients with paraneoplastic myasthenia gravis) have pathogenic potential. However, IgGs specific for intracellular antigens (eg, antineuronal nuclear antibody 1 [anti-Hu] associated with sensory neuronopathy and small cell lung cancer) are surrogate markers for CD8⁺ T lymphocytes targeting peptides derived from nuclear or cytoplasmic proteins. In an inflammatory milieu, those peptides translocate to neural plasma membranes as major histocompatibility complex class I protein complexes. Paraneoplastic neurologic autoimmunity can affect any level of the neuraxis and may be mistaken for cancer progression. Importantly, these disorders generally respond favorably to early-initiated immunotherapy and cancer treatment. Small cell lung cancer and thymoma are commonly associated with neurologic autoimmunity, but in the context of checkpoint inhibitor therapy, other malignancy associations are increasingly recognized.     

纵隔梭形细胞脂肪瘤1例

患者男,35岁,多囊肾病史30年,查体发现左侧中纵隔占位1周。体格检查:左侧下胸部听诊呼吸音减弱,叩诊左下胸部呈实音。X线平片:左下纵隔旁见类圆形软组织密度影,边缘清楚,左肺下叶受压外移。胸部CT:左侧纵隔心缘旁见类圆形混杂密度影,约15cm×14cm×12cm,病灶内见局灶性脂肪密度区,CT值约-110HU,大部为软组织密度区,其内密度不均匀,病灶边界清晰,邻近左肺下叶受压实变、外移(图1A);增强扫描病灶内脂肪部分未见强化,软组织部分呈轻度不均匀强     

An Overview of Immune Checkpoint Inhibitors in Gynecologic Cancers

Purpose

The goal of this study was to compile a review of topics pertinent to the use of immune checkpoint inhibitors in gynecologic malignancies, including foundation for use, current agents available and trials in gynecologic cancers, special populations of interest, identification and management of toxicities, and considerations in predictive biomarkers and response assessment.

Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes

OBJECTIVEType 1 diabetes mellitus (T1DM) is a rare, irreversible immune-related adverse event reported in patients receiving treatment with immune checkpoint inhibitors (ICI). However, clinical risk factors for ICI-induced T1DM (ICI-T1DM) and its impact on survival in patients remain unknown.RESEARCH DESIGN AND METHODSWe used Optum’s Clinformatics Data Mart database for assessment of the incidence and characteristics of T1DM in a large de-identified cohort of patients treated with ICI between 2017 and 2020. We applied Fine-Gray and cause-specific hazard models to study associations between patient/treatment characteristics and ICI-T1DM and applied the Cox model with ICI-T1DM as a time-varying covariate to assess the impact of ICI-T1DM on survival.RESULTSICI-T1DM was observed in 261 of 30,337 (0.86%) patients. Dual use of antibodies to cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) was associated with increasing risk of ICI-T1DM (hazard ratio [HR] 1.62; 95% CI 1.15–2.26) vs. anti–PD-L1 or anti–PD-1 alone. Younger age (HR 1.19 for every 5-year decrease; 95% CI 1.13–1.25) and preexisting non-T1DM diabetes (HR 4.48; 95% CI 3.45–5.83) were also associated with higher risk of ICI-T1DM. Conversely, prior use of immunosuppressive medications (HR 0.57; 95% CI 0.34–0.95) was associated with lower incidence of ICI-T1DM, but part of its protective effect may be due to the increased mortality rate. Development of ICI-T1DM does not seem to significantly impact patient survival.CONCLUSIONSThe risk of ICI-T1DM is associated with the type of ICI therapy, patient age, and preexisting non-T1DM diabetes. These data may help guide risk assessment and screening practices for patients during ICI therapy.     

非小细胞肺癌免疫检查点抑制剂治疗进展

肺癌是全球范围内发病率及死亡率极高的恶性肿瘤,其中以非小细胞肺癌(non-small cell lung cancer,NSCLC)最为常见。NSCLC的传统治疗主要依靠化学药物,近年来免疫治疗成为NSCLC治疗的热点,并取得了令人瞩目的进展。大量新型生物免疫制剂被开发并应用于临床,其中免疫检查点抑制剂的应用最广、疗效最为肯定。本文将对近年NSCLC免疫治疗生物标志物研究现状及进展进行阐述,以期提高免疫治疗精准度,更好地指导NSCLC患者的个体化治疗。     

梭形细胞肿瘤临床病理与免疫组化特性探讨

目的探讨梭形细胞肿瘤临床病理与免疫组化特性及病理诊断。方法应用免疫组化对34例梭形细胞肿瘤进行回顾性分析。结果梭形细胞肉瘤17例占50％，梭形细胞癌肉瘤10例占26．47％，梭形细胞癌5例占14．70％，其他诊断2例占9、83％。免疫组化31例表达Vim，21例表达CK，14例表达EMA、Actin，8例表达CD117、S-100，7例表达CEA、SM、CD34。CK与Vim同时表达18例，分别表达8例，Vim与CD117同时表达8例，仅CK、EMA、CEA表达3例。结论不同部位的梭形细胞肿瘤，形态学有其病理组织学特征，免疫组化同一梭形细胞肿瘤可有不同或相同抗体表达，不同类型梭形细胞肿瘤可有相同抗体表达，灶性表达非上皮组织来源肿瘤多由分化或转分化而来，结合免疫组化检测可提高病理诊断准确率。     

Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma

ObjectiveTo provide an overview for oncology nurses about Merkel cell carcinoma and its management with immunotherapy.Data SourcesA literature search was conducted from 2013 to the present using search terms including “Merkel cell carcinoma,” “avelumab,” “pembrolizumab,” “immune-mediated adverse events,” and “infusion-related reactions.” Clinical experience of the authors was also considered.ConclusionOncology nurses can expect to manage an increasing number of patients with Merkel cell carcinoma because of increased incidence of the disease, as well as evolving immunotherapy treatment paradigms. Both avelumab and pembrolizumab possess favorable safety profiles but are associated with immune-mediated and infusion-related reactions.Implications for Nursing PracticeOncology nurses need to understand Merkel cell carcinoma and be able to recognize the signs and symptoms of immune-mediated adverse events and infusion-related reactions associated with treatment to provide early intervention.     

腺垂体梭形细胞嗜酸细胞瘤临床病理观察

目的探讨腺垂体梭形细胞嗜酸细胞瘤的临床病理特征、诊断及鉴别诊断要点。方法对1例鞍区腺垂体梭形细胞嗜酸细胞瘤的临床表现、影像学特征、组织形态学、免疫表型及超微结构进行分析,并复习相关文献。结果患者女性,26岁。视力下降3年,停经2年半。影像学提示鞍区占位,术前拟诊为“脑膜瘤”。光镜下梭形肿瘤细胞呈束状或不规则排列,胞质丰富,嗜酸性,局部区域明显黏液变性,间质散在或小灶性淋巴细胞浸润。肿瘤细胞vimentin、S-100和EMA（＋）,Ki-67标记指数〈1％。电镜下以瘤细胞胞质内大量肿胀的线粒体为特征,缺乏分泌颗粒。结论腺垂体梭形细胞嗜酸细胞瘤是罕见的鞍区肿瘤之一,应与鞍区的其他梭形细胞肿瘤相鉴别,熟悉其临床病理特征,依靠免疫组化和电镜可确诊。     

睡眠梭产生机制及功能研究进展

睡眠梭是非快速动眼睡眠显著特征性脑电形式之一,但其特征亦复杂多变,在不多年龄、不同疾病中有不同表现。其产生与丘脑核团关系密切,但丘脑外核团也参与调控。睡眠梭在睡眠稳定、学习记忆、脑发育等诸多方面有着重要作用。本文对睡眠梭重要特征、产生机制及重要功能在近年的研究进展作综述。