头颈部鳞癌相关生物标志物与免疫治疗预后的关系

头颈部鳞癌(HNSCC)是世界上第六大常见的恶性肿瘤,每年发病超过55万,死亡超过30万人,吸烟和饮酒是其主要危险因素.HNSCC的治疗方案主要是基于TNM分期、以外科手术为主的综合疗法(放疗、化疗及生物治疗).对于HNSCC的治疗,其5年生存率近年来一直没有改善,因此,需要新的治疗方法提高患者生存率,改善患者生活质量...     

Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC....     

“Cold” colorectal cancer faces a bottleneck in immunotherapy

The advent of immunotherapy and the development of immune checkpoint inhibitors(ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically “hot” tumors.However, for immunologically “cold” tumors such as colorectal cancer(CRC),only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and lo...     

Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma

BACKGROUND The expression of brain cytoplasmic RNA1(BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma(HCC) is one of the most frequent types of cancer worldwide.AIM To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis.METHODS Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinico...     

G蛋白偶联雌激素受体在免疫调节中作用的研究进展

近年来研究发现,G蛋白偶联雌激素受体（GPER）不同于传统的核受体,是第三种独立作用的雌激素受体,它属于七次跨膜的G蛋白偶联受体（GPCR）家族成员。雌激素通过GPER介导G蛋白信号通路活化从而在正常生理及多种异常疾病中扮演重要角色,包括癌症、心血管疾病和炎症性疾病等。GPER表达于多种免疫细胞中,通过增强免疫细胞活性或调节免疫细胞之间的互动从而在免疫反应中发挥作用。同样,GPER还可参与炎症因子相关基因的表达从而抑制炎症反应。近期研究进一步揭示GPER不仅参与正常免疫系统的维持、异常免疫性疾病及炎症性病变,而且在肿瘤免疫调节中或有重要价值。笔者研究团队前期在多种恶性肿瘤中证实GPER介导的下游信号通路及其生物学功能,并发现GPER在乳腺癌和肝癌的肿瘤微环境中可能通过能量代谢重塑调节肿瘤免疫,以及血液肿瘤免疫治疗中靶向GPER有协同抗肿瘤药物的正向作用。综合现有研究发现,GPER可通过多样化的调节方式参与多种癌症的肿瘤免疫过程,包括乳腺癌中GPER通过调节免疫检查点分子的表达影响肿瘤免疫逃逸;肝癌中GPER调节免疫微环境和免疫细胞浸润,增加细胞因子和趋化因子的产生影响肿瘤免疫调节;结直肠癌中GPER增强免疫细胞的抗肿瘤活性和促进免疫细胞的细胞毒杀伤能力;血液肿瘤中GPER影响不同免疫细胞之间的“交叉对话”增强抗肿瘤免疫治疗等。因此,GPER为免疫相关疾病的治疗发展提供了新的途径,尽管目前尚处于探索阶段,但GPER作为新靶点联合免疫检查点抑制剂等药物的研发充满了临床潜力。本文综述当前GPER相关免疫调节作用的研究进展,为相关的基础与临床研究提供参考。     

负载自体肿瘤细胞裂解物的DC疫苗联合CIK治疗晚期肾癌的临床观察--附10例报告

背景与目的:肾癌的主要治疗手段是手术,但晚期肾癌术后复发率高,加上肾癌对化疗和放疗不敏感,因此,晚期肾癌预后不佳,需要寻找新的更有效的治疗方法。本研究通过负载自体肿瘤细胞裂解物的树突细胞(dendriticcells,DC)疫苗联合细胞因子诱导的杀伤细胞(cytokine-inducedkillercells,CIK)治疗10例晚期肾癌,观察近期的临床疗效,免疫学反应及副作用。方法:分离患者外周血单核细胞,体外经GM-CSF和IL-4诱导产生DC细胞,并负载自体肿瘤细胞裂解物;T淋巴细胞经IFN-γ、IL-2、CD3单抗、IL-1α体外诱导产生CIK细胞。所有患者在切除原发病灶后,接受每周一次的皮内DC疫苗注射治疗,至少8次治疗;CIK细胞过继细胞免疫治疗,每2周一次,至少接受4次治疗。临床疗效和免疫学反应分别通过影象学检查,外周血T淋巴细胞亚群改变和迟发性超敏(delayed-typehypersensitivity,DTH)反应进行评估。结果:(1)4例有可评价病灶的患者中1例部分缓解(PR),2例疾病稳定(SD),1例进展(PD);6例没有可评价病灶的患者中1例PD,1例失访,另外4例未见疾病进展。随访时间6～20个月(中位时间11个月)。(2)与治疗前比较,治疗2个月后患者CD3 、CD4 、CD4 /CD8 、CD56 明显升高(P<0.05)。(3)包括PR患者在内的6例患者DTH反应呈现阳性。(4)除一过性的发热、畏寒外没有其它不良反应出现。结论:负载自体肿瘤细胞裂解物的DC疫苗联合CIK细胞治疗晚期肾癌有一定的近期临床疗效,能诱导出特异的抗肾癌免疫反应,并且有良好的耐受性。     

甲状腺未分化癌靶向治疗研究进展

甲状腺未分化癌（ATC）是一种恶性程度高、侵袭性强的甲状腺恶性肿瘤，发病迅速，预后差，目前尚缺乏有效治疗手段。分子靶向治疗为ATC治疗提供了一种新思路。酪氨酸激酶抑制剂乐伐替尼在治疗ATC患者临床试验中疗效良好；鼠类肉瘤病毒癌基因同源物B1（ BRAF）基因抑制剂达拉非尼联合曲美替尼治疗 BRAF ^V600E 阳性ATC患者的有效性已在临床试验中得到证实，2021年美国国家综合癌症网络甲状腺癌临床实践指南中提出达拉非尼联合曲美替尼可作为治疗 BRAF ^V600E 阳性ATC患者治疗的首选方式；免疫检查点抑制剂帕博利珠单抗应用于高肿瘤突变负荷甲状腺癌治疗，可作为程序性死亡蛋白1高表达ATC患者的首选方式；哺乳动物雷帕霉素靶蛋白通路抑制剂、过氧化物酶体增殖物激活受体γ激动剂、靶向内皮生长因子受体的单克隆抗体西妥昔单抗及新型血管阻断剂康布瑞汀磷酸二钠仍处于临床研究阶段。本文综述了目前ATC靶向药物治疗的研究进展。     

Progressive supranuclear palsy: Advances in diagnosis and management

Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease with no current cure or disease modulating therapies that can only be definitively confirmed at autopsy. Growing understanding of the phenotypic diversity of PSP has led to expanded clinical criteria and new insights into etiopathogenesis that coupled with improved in vivo biomarkers makes increased access to current clinical trials possible. Current standard-of-care treatment of PSP is multidisciplinary, supportive and symptomatic, and several trials of potentially disease modulating agents have already been completed with disappointing results. Current ongoing clinical trials target the abnormal aggregation of tau through a variety of mechanisms including immunotherapy and gene therapy offer a more direct method of treatment. Here we review PSP clinicopathologic correlations, in vivo biomarkers including MRI, PET, and CSF biomarkers. We additionally review current pharmacologic and non-pharmacologic methods of treatment, prior and ongoing clinical trials in PSP. Newly expanded clinical criteria and improved specific biomarkers will aid in identifying patients with PSP earlier and more accurately and expand access to these potentially beneficial clinical trials.     

胰腺癌免疫治疗的现状及前景CSCD

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断探索中。目前针对胰腺癌独特的肿瘤微环境设计了多种免疫治疗策略,包括强化/提高自身免疫反应(免疫调节剂、单克隆抗体、肿瘤疫苗和细胞治疗)以及抑制肿瘤免疫逃逸(免疫检查点抑制剂和肿瘤微环境)等。本文就胰腺癌免疫治疗的研究进展进行综述,着重探讨PD-1/PD-L1抑制剂在胰腺癌中的应用,并分析免疫治疗联合其他方式治疗胰腺癌的前景。