免疫检查点抑制剂相关肺炎研究进展

随着癌症生物学和发病机制研究的不断深入,免疫检查点抑制剂（ICIs）得以问世,为晚期肿瘤患者带来了新的生存希望,从而开启了癌症免疫治疗的新时代,但随着免疫治疗在临床上的广泛应用,免疫相关不良事件（irAEs）也逐渐显现出来,并广泛为一线临床医师所熟知。免疫检查点抑制剂可激活T细胞攻击体内的正常组织和器官,并导致多种不良反应。而免疫检查点抑制剂相关肺炎（CIP）是irAEs中较为罕见且预后较差的并发症之一。本文参考目前国内外相关文献,就部分ICIs的治疗机制及CIP的发病率、危险因素、发生机制、临床表现、影像学表现与CIP的分级及治疗管理作一综述。     

免疫检查点抑制剂相关肺炎危险因素及管理策略的研究进展

近年来,随着免疫检查点抑制剂（immune checkpoint inhibitors,ICIs）在肿瘤治疗中的广泛应用,免疫治疗相关不良反应逐渐引起人们的关注。免疫检查点抑制剂相关肺炎（checkpoint inhibitor pneumonitis,CIP）是相对少见的免疫治疗相关肺毒性,也是引起ICIs相关死亡的重要原因之一。积极探索CIP的相关危险因素,甄别出发生CIP的高危人群,有利于CIP的早期诊断、及时治疗。故本文就CIP的危险因素及管理策略研究进展进行综述,以提高临床医生对该不良反应的认识。     

免疫检查点抑制剂治疗小细胞肺癌疗效及预后生物标志物的研究进展

小细胞肺癌（SCLC）的治疗已经迈入免疫治疗时代,免疫疗法联合化疗的一线治疗新标准得以确立。然而并非所有 SCLC患者均能从免疫检查点抑制剂（ICI）中获益,缺乏有效的疗效和患者预后生物标志物在很大程度上限制了其临床应用。目 前,肿瘤相关生物标志物PD-L1表达水平在预测SCLC免疫治疗疗效及患者预后中最为常用;肿瘤突变负荷（TMB）、错配修复缺 陷（dMMR） 和微卫星高度不稳定（MSI-H）也可作为预测 ICI 治疗疗效及患者预后的潜在生物标志物。而 dMMR/MSI-H 因在 SCLC中的发生频率极低,限制了其应用;外周血免疫相关标志物因其便捷性而在SCLC免疫治疗中受到越来越多的关注;肿瘤 微环境相关的生物标志物也有助于识别从ICI治疗中获益的患者。因此,深入了解SCLC的一线免疫治疗现状和预测患者免疫 治疗疗效与预后的潜在生物标志物的研究进展,可为SCLC患者免疫治疗优化策略和分层管理提供思路和参考。     

免疫检查点抑制剂相关甲状腺毒性研究进展

免疫检查点抑制剂（ICIs）作为肿瘤免疫治疗的一种强效抗癌方式越来越多地应用到肿瘤治疗中。其通过解除肿瘤细胞对于机体免疫细胞的抑制作用达到杀伤肿瘤细胞的作用，但在作用过程中由于过度激活免疫细胞引发机体包括内分泌系统在内的多个系统出现自身免疫反应，即免疫相关不良事件（irAEs）。甲状腺毒性是比较常见的内分泌毒性，包括甲状腺功能减退、甲状腺功能亢进、甲状腺炎甚至甲状腺危象等。随着临床上ICIs的广泛应用，甲状腺毒性的发生势必越来越多，现就其流行病学、发病机制、临床表现及临床管理方面做如下综述，以提高临床医生的认识，改善癌症患者的生存质量。     

20例晚期肿瘤患者免疫检查点抑制剂不良反应临床观察并文献复习

目的观察免疫检查点抑制剂治疗的相关不良反应。方法回顾性分析2017年3月—2019年8月在中国医学科学院肿瘤医院进行免疫检查点抑制剂治疗的20例晚期肿瘤患者临床资料,总结免疫检查点抑制剂治疗的相关不良反应。结果 20例患者免疫治疗中位时间为4.0月,发生较明确免疫治疗相关不良反应的共6例,中位时间5.3月,其中1例发生Ⅰ级免疫性胃肠炎,1例Ⅰ级免疫性皮炎,1例Ⅱ级免疫性甲状腺炎,1例Ⅲ级免疫性肝炎,1例Ⅲ级免疫性肺炎及1例Ⅳ级免疫性肺炎。结论伴随免疫治疗的相关不良反应发生率较高,严重的不良反应甚至危及生命,故免疫相关不良反应的早发现、早诊断及早干预至关重要。     

实体瘤局部免疫治疗的探索与发展现状

免疫治疗已被证实为极具前景的晚期恶性实体瘤治疗方式之一。肿瘤所致免疫激活和免疫效应主要来自肿瘤抗原与肿瘤微环境（tumor microenvironment,TME）的相互作用,而肿瘤抗原的免疫原性减弱与免疫应答通路缺陷是产生免疫逃逸的主要原因。免疫治疗通过不同途径增强抗原提呈能力,激活免疫应答及改善TME的免疫抑制状态,提高患者生存获益。由于免疫治疗疗效与药物浓度呈正相关,往往较高的治疗剂量才有效,但这对机体将造成不同程度的免疫相关毒性反应及诱导耐药产生。因此,一种新的治疗方式-局部免疫治疗,被探索并取得了早期临床疗效。本文就几种常见的不同类型免疫药物在局部治疗中的作用机制、应用特点及临床发展现状进行综述。      

免疫检查点抑制剂在肝细胞癌治疗中的研究进展

肝细胞癌（HCC）是癌症相关死亡的最常见原因之一，大多数HCC患者在癌症晚期被诊断出来。2017年以前，治疗晚期HCC的药物主要是酪氨酸激酶抑制剂，随着免疫检查点抑制剂（ICIs）的出现，免疫治疗逐渐给此类患者带来新希望。目前，ICIs与其他全身或局部治疗的联合方案已成为治疗晚期HCC最有潜力的策略，其中一些药物已进行大规模临床试验。晚期HCC免疫治疗的主要挑战包括预测性生物标志物的探索、免疫相关不良事件（irAEs）的管理以及发掘更有效的联合方案等。本文旨在对肝细胞癌ICIs单药或联合用药以及其他免疫治疗的最新进展进行综述，并讨论目前研究与临床应用的限制和未来发展方向。     

非小细胞肺癌免疫治疗研究进展

近年来,肺癌的治疗手段层出不穷,从传统化疗到靶向药物,再到免疫检查点抑制剂的出现,很大程度上改善了患者的预后,延长了患者生存期。免疫检查点抑制剂的应用,即免疫治疗,一改传统的治疗方式,作用于程序性细胞死亡蛋白-1（PD-1）及其配体（PD-L1）发挥有效且持久的抗肿瘤反应。本文主要介绍了近年来免疫治疗一线、二线应用于非小细胞肺癌（NSCLC）的研究情况,影响免疫治疗疗效的因素,及免疫治疗的相关毒副反应。     

免疫检查点抑制剂相关肺炎的诊治进展北大核心

过去的几年中,免疫治疗在肿瘤治疗领域取得了不可忽视的成绩,为肿瘤患者带来了新的希望,但免疫检查点抑制剂在阻断肿瘤细胞免疫逃逸的同时,也可能导致免疫耐受失衡,发生免疫相关不良反应。免疫检查点抑制剂相关肺炎是免疫检查点抑制剂应用过程中出现的免疫相关性不良反应之一,此类不良反应临床症状、影像学表现及病理表现均不典型,且有潜在的致死性,增加患者的死亡率。随着免疫检查抑制剂越来越多的投入临床,相关病例也逐渐增多,需要临床医生对高危患者密切观察,疑有免疫检查点抑制剂相关肺炎发生时及时识别、尽早做出相应的处理,并在此类肺炎痊愈后谨慎评估是否可以继续使用免疫治疗。本文就其临床表现、诊断及治疗等作一综述,以提高临床医生对此类药物治疗引起的免疫相关性肺炎的认识,为此类药物的临床应用提供参考。     

锌指蛋白调控肿瘤免疫原性的作用及其机制的研究进展

寻找对肿瘤免疫原性具有关键调控作用的生物治疗靶点是抑制肿瘤免疫逃逸、提高肿瘤免疫治疗效果的关键。锌指蛋白（ZFP）通过与DNA、RNA、蛋白质的相互作用,调控肿瘤抗原的形成、肿瘤表面MHC分子及其共刺激分子的表达、损伤相关分子模式的释放等,影响肿瘤细胞的免疫原性及肿瘤微环境（TME）中免疫细胞的分布和功能,进而在调节抗肿瘤免疫应答和肿瘤免疫逃逸中发挥重要作用。近年来,临床前及临床研究探索将ZFP 相关的生物治疗方法应用于肿瘤免疫治疗,主要聚焦在免疫检查点阻断治疗、免疫细胞治疗,以及免疫治疗联合治疗策略展现出了可喜的应用前景。     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.