TCRγδ/δ2在结直肠癌患者外周血和肿瘤组织中的表达及相关性

目的 检测TCRαβ、TCRγδ及TCRδ2在结直肠癌患者外周血和肿瘤组织中的表达和相关性,为以γδT细胞为基础的免疫治疗提供依据.方法 使用流式细胞仪检测TCRαβ、TCRγδ及TCR δ2三者在结直肠癌患者外周血、正常肠道粘膜组织、癌旁组织及癌组织中的表达;分析结直肠癌患者外周血中TCRδ2与组织中TCRγδ和TCRδ2表达水平的相关性.结果 外周血中TCRγδ和TCRδ2在结直肠癌组中表达高于对照组（P＜0.05）.TCRγδ和TCRδ2在癌旁组织和癌组织中的表达高于正常肠道粘膜组织（P＜0.05）.当外周血TCRδ2升高到较高水平时,癌旁组织中TCRγδ和TCRδ2水平同步升高（P＜0.05）,而癌组织中TCRγδ和TCRδ2水平反而降低（P＜0.05）.结论 结直肠癌患者外周血Vδ2T细胞的水平与癌组织中浸润的γδT细胞和Vδ2T细胞具有相关关系,为Vδ2T细胞的局部介入治疗提供了理论依据.     

Clinical and pathologic features correlated with rare favorable survival in patients with BRAFV600E mutated colorectal cancer

BackgroundBRAF^V600E mutations occur in fewer than 10% of all patients with metastatic colorectal cancer (CRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for patients with BRAF^V600E mutated metastatic CRC in general are poor. Characteristics distinguishing patients with BRAF^V600E mutated metastatic CRC with favorable versus unfavorable outcomes have not been well annotated.MethodsRecords of 187 patients with BRAF^V600E mutated metastatic CRC evaluated at MD Anderson Cancer Center between 2005–2020 were reviewed. Patients with the shortest and longest metastatic survival (N=25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing.ResultsMedian metastatic survival differed between the 2 BRAF^V600E mutated metastatic CRC populations (8.6 vs. 83.9 months, hazard ratio 32; P<0.0001). Patients with poor survival more commonly had hepatic involvement [75% vs. 28%, odds ratio (OR) 8.1, 95% confidence interval (CI): 2.3–29; P=0.001]. Patients with favorable survival were more likely to develop metachronous metastases (52% vs. 16%, OR 5.7, 95% CI: 1.5–21; P=0.01) and undergo definitive locoregional therapy to metastatic disease (40% vs. 0%, OR 34.5, 95% CI: 1.9–630; P=0.01). Microsatellite instability (36% vs. 4%, OR 19.8, 95% CI: 2.2–180; P=0.008) and prior tobacco exposure (44% vs. 16%, OR 4.1, 95% CI: 1.1–15.6, P=0.04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies and immunotherapy were noted in the favorable group.ConclusionsA small fraction of patients with BRAF^V600E mutated metastatic CRC can achieve excellent long-term survival which belies conventional context and is driven by either surgical metastectomy or by systemic treatment options. While poor overall prognosis remains the recognized outcome for most patients with BRAF^V600E mutated metastatic CRC, it is possible that few may achieve exceptionally favorable survival.     

Clinical Study on General lmmunotherapy of Hepatocellular Carcinoma

In the present study,67 cases of hepatocellular carcinoma(HCC)were treated withimmunotherapy or immunochernotherapy.The results indicated that natural killer cell(NK)andantibody-dependent cytotoxicity cell(ADCC)activities and lymphocyte transformation rate(LTR)were significantly improved in vivo after treatment.The NK activity in tumor tissue,which showed aheavy immunosuppression,could also be enhanced and recovered to normal level after treatment withlymphokine mixture and 5-fluorouracil(5-FU).Immunity of host with postoperativeimmunochemotherapy was rapidly improved and recovery vate was high.The survival time in thesecases of unresectable tumors was obviously prolonged when a general immunotherapy was used.Immunochemotherapy can impr(?)ve immunity and inhibit selectively Ts cells as well as kill directly thetremor cells;therefore,it can play an important role in the treatment of hepatocellular carcinomaand in the prevention of its recurrence after operation.     

HLA-肽四聚体和过继性免疫疗法在防止巨细胞病毒疾病中的应用

背景：抗病毒药物能减少早期的巨细胞病毒疾病,但有较强的毒性和引起晚期巨细胞病毒疾病发生的可能。为了更好地防治巨细胞病毒疾病,研究细胞毒性T淋巴细胞控制巨细胞病毒再活化的作用是很关键的,荧光HLA-肽四聚体是一个很好的工具,被用来监测移植受者的巨细胞病毒特异细胞毒性T淋巴细胞的恢复。 目的：探讨HLA-肽四聚体和过继性免疫疗法在治疗巨细胞病毒疾病中的作用。 方法：由第一、二作者检索2003/2009 PubMed数据库及万方数据库有关移植后巨细胞病毒特异细胞毒性T淋巴细胞检测、抗病毒药物应用、HLA肽四聚体应用、过继性免疫治疗作用的文献,英文检索词为“HLA-peptide tetramers, cytomegalovirus, specific CTL, adoptive immunotherapy”,中文检索词为“HLA-肽四聚体,巨细胞病毒,特异细胞毒性T淋巴细胞,过继性免疫治疗”。排除重复性研究,纳入29篇归纳总结。 结果与结论：用巨细胞病毒特异细胞毒性T淋巴细胞进行的过继性免疫治疗是非常完美的策略,然而,产生这些细胞是昂贵和耗时的,因此治疗不是在每个移植中心都能进行。用HLA-肽四聚体从巨细胞病毒血清阳性供者外周血中选择巨细胞病毒特异细胞毒性T淋巴细胞是非常有希望的策略,使过继性免疫疗法更容易进行。 关键词：HLA-肽四聚体;过继性免疫治疗;巨细胞病毒疾病;特异T细胞;细胞毒性T淋巴细胞     

γδT细胞对血液肿瘤细胞的体外杀伤活性

目的:建立γδT细胞培养体系,探讨γδT细胞对不同血液肿瘤细胞的杀伤活性.方法:选取2016年1月至2016年4月在解放军第307医院造血于细胞移植科收治的4例B细胞淋巴瘤患者和该院5例体检健康志愿者,分别分离其外周血单个核细胞(peripheral blood mononuclear cell,PBMC),用唑来磷酸(zoledronate,Zol)和IL-2体外扩增γδT细胞,采用流式细胞术检测γδT细胞对血液肿瘤细胞Jurkat、THP-1、HL-60、K562、Raji、U-937和RPMI-8226的杀伤活性,比较CIK、NK和γδT三种细胞对K562细胞的杀伤作用,检测γδT细胞IFN-γ、TNF-α的分泌水平及CD107a分子的表达水平.结果:成功在体外扩增外周血γδT细胞;γδT细胞对Jurkat、THP-1、HL-60、K562、U-937和RPMI-8226细胞均有明显的杀伤活性(P＜0.05);γδT细胞对K562细胞的杀伤活性与NK细胞无统计学差异,但明显强于CIK细胞(P＜0.01);随着与K562细胞共孵育时间的延长,γδT细胞分泌IFN-γ的水平呈现出时间依赖性增加,TNF-α在8h后逐渐增加;与K562细胞或HL-60细胞共孵育后,γδT细胞CD107a分子的表达水平均显著增加(P＜0.01).结论:体外扩增的γδT细胞对血液肿瘤细胞具有较高的杀伤活性,为血液肿瘤的细胞免疫治疗提供实验依据.     

Mechanisms of Sublingual Immunotherapy

Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolerated treatment for allergic rhinitis. Emerging treatment strategies are also aimed at the primary treatment of allergic asthma, particularly allergy to house dust mites. Knowledge of the exact mechanisms of action of sublingual immunotherapy is at a basic level, although there appear to be similarities to the immunological changes seen in subcutaneous immunotherapy. An improved understanding should allow the development of more effective treatment programs and widen the potential use of this form of immunotherapy. This review discusses the possible mechanism of action of sublingual immunotherapy, including data from animal and clinical studies, while comparing this with the current understanding of subcutaneous immunotherapy.     

肺癌免疫治疗的临床研究进展

目前免疫治疗在晚期肺癌的应用已经进入一线方案,尤其是肺癌的特异性免疫治疗进展迅速,如程序性死亡受体/配体-1(programmed death receptor 1/ligand 1,PD-1/L1)、细胞毒性T淋巴细胞抗原-4(cytotoxic T-lymphocyte antigen 4,CTLA-4)、吲哚胺-2,3-双加氧酶(indoleamine2,3-dioxygenase,IDO)等检查点抑制剂先后进入临床试验或临床应用,且已证实具有明显生存获益,为肺癌的临床治疗带来了新的曙光,但在适宜人群和不良反应方面仍存在限制性,而且肺癌术后复发转移的防治仍有待深入研究。未来在双免疫药物的联合应用、新辅助免疫治疗、过继性免疫治疗、以及免疫和放化疗的结合方案优化等方向将是临床试验的热点,有望使肺癌的临床疗效得到进一步提高。     

Immune alterations in malignant melanoma and current immunotherapy concepts

Introduction: Malignant melanoma is a highly aggressive, immunogenic tumor that has the ability to modulate the immune system to its own advantage. Patients with melanoma present numerous cellular immune defects and cytokine abnormalities, all leading to suppression of the host anti-tumor immune response. Innovative treatment strategies can be achieved through employing our knowledge of the melanoma-induced immune alterations.

Areas covered: The authors review comprehensively the immune abnormalities in individuals with melanoma, and provide a summary of currently available melanoma immunotherapy agents that are currently on the market or undergoing clinical trials.

Expert opinion: Ipilimumab, a monoclonal antibody directed against the CTLA-4, is one of the current forefront treatment strategies in malignant melanoma. Novel immunomodulating agents have shown clear activity in patients with malignant melanoma. These include anti-PD-1 and anti-PD-1 ligand antibodies that may soon become important items in the anti-melanoma armamentarium. Combinations of different immunotherapy agents, between themselves or with other agents, are currently being studied in an attempt to further enhance the antineoplastic effect in patients with malignant melanoma.     

Immunotherapy of hypersensitivity to hymenoptera venom

Insect sting allergy is a common condition with a risk of life-threatening anaphylaxis. After a severe reaction, the fear of being restung can significantly reduce quality of life. Venom immunotherapy (VIT) is a highly effective treatment of the underlying type I-sensitisation. This review addresses the mechanisms of immune modulation by VIT and outlines current clinical application. Although highly effective in the majority of patients, VIT fails in a few individuals. It can also cause systemic allergic side effects, restricting its application to physicians trained in the treatment of anaphylaxis. This review discusses several new strategies to overcome these problems, which are presently a promising focus of research. These include the use of new adjuvants, of recombinant and genetically engineered venom allergens, as well as vaccination with peptides.