转移性胰腺癌的联合免疫治疗研究进展

胰腺癌是恶性程度极高的消化系统肿瘤，特别是转移性胰腺癌在临床上表现为病程短、进展快、病死率高等特点。尽管吉西他滨已成为晚期胰腺癌的标准治疗方案，但治疗效果仍未达到预期。因此临床上逐渐开展以放化疗、免疫治疗、靶向治疗以及纳米技术等多种治疗手段，但目前对于转移性胰腺癌单药治疗效果欠佳，研究人员考虑采用联合治疗不断探索新的治疗方案，在临床与基础研究方面进行了多项针对转移性胰腺癌的联合免疫治疗试验，但总体来讲该领域的治疗方案目前仍存在争议，本文就近年来转移性胰腺癌的联合免疫治疗研究进展作一综述。     

肿瘤免疫治疗的研究进展

近年来肿瘤的免疫治疗越来越受到重视.肿瘤免疫治疗的目的是激发或调动机体的免疫系统,增强肿瘤微环境的抗肿瘤免疫力,从而控制和杀伤肿瘤细胞.目前肿瘤的免疫疗法主要包括肿瘤疫苗、细胞因子治疗、单克隆抗体技术和细胞过继免疫治疗.     

乳腺癌的免疫治疗

免疫治疗在乳腺癌的综合治疗中日益受到重视。本文简要综述了单克隆抗体及肿瘤疫苗在乳腺癌免疫治疗中的研究进展。     

肿瘤免疫治疗:回顾与展望

随着肿瘤免疫学的迅速发展, 免疫治疗逐渐引起肿瘤治疗领域专家的重视, 相关研究为晚期肿瘤患者提供了新的治疗机会。以程序性死亡受体1及其配体、细胞毒性T淋巴细胞相关抗原4为代表的免疫检查点抑制剂是目前晚期肿瘤临床治疗的研究热点, 已有多种免疫检查点抑制剂获得美国食品药品监督管理局批准用于晚期肿瘤免疫治疗, 其不仅安全性高, 且在晚期黑色素瘤、非小细胞肺癌、肾癌、尿路上皮癌、非霍奇金淋巴瘤中展现出令人振奋的治疗效果, 有效延长了患者生存期。嵌合抗原受体T细胞疗法也是目前免疫治疗领域的明星产品之一, 对急性白血病、非霍奇金淋巴瘤等血液系统恶性肿瘤展现出强大持久的治疗效果, 以Simpuleucel-T为代表的肿瘤疫苗曾一度成为肿瘤免疫治疗里程碑式的成功范例。肿瘤免疫治疗已取得了突破性进展, 研究前景不可估量。     

树突状细胞与消化系统肿瘤免疫治疗的研究进展

树突状细胞（dendritic cell,DC）是体内功能最强的专职抗原递呈细胞（antigen presenting cell,APC）,在抗肿瘤免疫应答中起关键作用。近年研究表明,肿瘤可使DC功能失常、凋亡及免疫反应中的信号转导分子缺失,目前以DC为基础的抗消化系统肿瘤免疫治疗作为传统治疗的重要辅助手段发展迅速。本文就DC的生物学特性,与消化系统肿瘤的关系以及在抗肿瘤免疫治疗中的进展作一简要综述,为临床进一步研究提供佐证。     

肿瘤免疫逃逸与肿瘤免疫治疗的思考

机体抗肿瘤的免疫效应与肿瘤逃避免疫系统的攻击之间形成一对此消彼长的矛盾关系。近年来,人们针对肿瘤免疫逃逸的机制,致力于研究多种免疫治疗方案,以提高肿瘤的免疫原性,激发机体的特异性和非特异性免疫应答,促进肿瘤的消亡。癌基因的不断发现和深入研究、各种细胞因子和免疫刺激分子功能的不断拓展和深化,都为肿瘤的免疫治疗提供了强有力的理论基础。     

树突状细胞与血液肿瘤的免疫治疗

抗肿瘤免疫治疗是肿瘤治疗的一种重要手段 ,可分为非特异性免疫和特异性免疫。特异性免疫治疗是目前肿瘤免疫治疗的主要方向 ,其中抗原呈递细胞 (APC) ,主要是树突状细胞 (dendriticcells ,DC)治疗为近年来的研究热点。本文主要对DC特性 ,DC抗肿瘤机制及其与肿瘤免疫逃逸的关系以及近年来DC在肿瘤免疫治疗方面的进展综述如下。1　树突状细胞特性DC是机体免疫系统中一种最强有力的专职抗原呈递细胞 ,在免疫应答的启动、调控中起着关键作用[1] 。DC分化于CD+ 3 4 的造血祖细胞[2 ] ,有两个主要来源 :髓系DC和淋巴系DC。DC表面高表达…     

树突状细胞联合细胞因子诱导的杀伤细胞免疫治疗血液系统肿瘤的研究进展

近年来,随着恶性肿瘤的发病率逐年升高,其治疗方法在手术、放疗和化疗这些传统治疗基础上有了更多的进展,主要集中于细胞免疫治疗的方面,其中树突状细胞联合细胞因子诱导的杀伤细胞(DC-CIK)的免疫治疗对肿瘤患者的疗效肯定,在临床上表现出很好的抗肿瘤特性及重建与增强肿瘤患者的免疫系统的能力,具有潜在的应用价值。在以化疗为主、恶性度相对较高的血液系统肿瘤的治疗方面,DC-CIK细胞免疫治疗效果究竟如何呢?本综述检索2012至2018年的中英文文献并进一步聚焦于18篇关于血液系统肿瘤的临床研究型文献,深入系统分析DC-CIK细胞免疫治疗的特点和应用,发现DC-CIK细胞免疫治疗在血液系统肿瘤方面具有良好的临床疗效和应用价值,如果进一步规范流程、统一方案,其疗效会更加明显。为此,本文就DC和CIK细胞生物学特征、DC-CIK细胞免疫治疗在血液系统肿瘤的临床研究方面的进展进行综述。     

嵌合抗原受体-T细胞免疫治疗应用现状及相关实验室检查

嵌合抗原受体(CAR)T细胞免疫治疗是肿瘤治疗的一次革命, CAR-T细胞免疫治疗在B细胞白血病、淋巴瘤和多发性骨髓瘤的治疗中疗效显著, 但存在抗原逃逸、抗原异质性、毒副作用等不足, 在其他恶性血液肿瘤和实体肿瘤治疗中也面临诸多挑战。CAR-T细胞免疫治疗前后进行全面、持续的实验室指标检测对毒副作用的早期预警及治疗监测具有重要作用。未来需要不断改进CAR-T细胞的设计、优化治疗方案, 提高其抗肿瘤活性, 为肿瘤治疗带来新的突破。     

树突状细胞在白血病免疫治疗中的研究进展

树突状细胞(DC)是目前发现的体内最强专职抗原提呈细胞,在抗肿瘤免疫应答中,能将肿瘤抗原呈递给T细胞,引发机体产生抗肿瘤的免疫应答。利用DC制备肿瘤疫苗可望提供一种有效的白血病免疫治疗方法。本文主要介绍DC肿瘤疫苗在白血病免疫治疗中的研究进展。     

Biomarkers for cancer immunotherapy

Immune-biomarkers and -assays are important for development of cancer immunotherapy to select the patients who are expected to respond to immunotherapy before or early after immunotherapy, to monitor immune induction following immunotherapy, and to evaluate anti-tumor effects early after immunotherapy. Comprehensive immune-evaluation including positive and negative immune responses against cancer cells and identification of blood biomarkers which reflect immune-conditions in tumor microenvironment are required although direct evaluation of tumor tissues can be possible for some patients. Importance of immune responses has recently been recognized even for standard cancer treatments including chemotherapy and molecular target therapy. Therefore, immunological biomarkers may be useful for any cancer treatment.     

Hazards and complications of BCG immunotherapy.

The hazards and complications of BCG immunotherapy, as well as the potential for enhanced tumor growth, make it imperative that the clinician know the clinical setting in which BCG can offer therapeutic benefit. This would include the intratumor injection of localized intradermal tumor deposits of melanoma and breast cancer, chemoimmunotherapy with BCG to prolong remission in acute myelogenous leukemia, and possibly the use of BCG as an adjuvant to control minimal residual disease. Aside from these situations, it is advisable to treat patients only on clearly defined experimental protocols.     

The immunotherapy of patients with ovarian cancer

Ovarian cancer is a leading cause of cancer mortality. Chemotherapy is effective in reducing tumor burden in a majority of patients, however, only approximately 20% of advanced disease patients will ultimately survive tumor free, and further treatment options are needed. Continuing advances in immunology make immunotherapy a promising area for future research. The design of immunotherapy strategies for ovarian cancer requires an understanding of the immune microenvironment of the peritoneal cavity, which is frequently involved with ovarian cancer metastases and is the site of its most devastating effects. Immunotherapy approaches for ovarian cancer include locoregional and systemic cytokine therapies, prophylactic and therapeutic vaccines, and adoptive immunotherapy strategies. This review will summarize previous clinical trials as well as future directions for research. Further progress in T-cell specific immune responses will require the identification of specific ovarian cancer antigens that are processed and presented on the surface of tumor cells in the context of specific HLA molecules. In addition, a more detailed understanding of functional relations between the peritoneal microenvironment and the metastatic process is required.     

Clinical applications of virosomes in cancer immunotherapy

Cancer immunotherapy is increasingly accepted as a treatment option for advanced stage disease. The identification of tumour-associated antigens in 1991 has prompted the development of antigen-specific immunotherapeutic strategies for a variety of cancers. Many of them result in some immunological responses in cancer patients; however, clinical results were not observed concomitantly with immunological responses; therefore, further improvements in the field of immunotherapy are urgently needed. Virosomes are lipidic envelopes devoid of genetic information, but which retain the antigenic profile and fusogenic properties from their viral origin. Virosomes are versatile antigen carriers and can be engineered to perform various tasks in cancer immunotherapy. Preclinical data have fostered the development of innovative clinical protocols. Hence, immunopotentiating reconstituted influenza virosomes will be assessed in breast and melanoma immunotherapy, and may contribute to the development of clinically effective cancer vaccines and ultimately improve patient outcomes. The objective of this review is to provide an overview of the potential clinical applications of virosomes as innovative and potentially effective reagents in active specific cancer immunotherapy.     

BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma.

Results of our study suggest that BCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. BCG is more effective in patients with small amounts of subclinical disease. It is apparent from results of clinical trials that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. Hwever, until clinical trials are complete, this treatment as adjuvant therapy must be considered investigational.     

晚期肺癌免疫治疗现状及影像学疗效评价和预测

免疫治疗是近年新兴的治疗手段,为部分传统治疗疗效不佳的肿瘤患者提供新的治疗思路,已成为部分晚期肺癌患者的一线治疗方案。目前,实体瘤疗效评价标准(response evaluation criteria in solid tumors, RECIST)仍是实体瘤疗效评价的主流标准。但免疫治疗因其治疗反应的特殊性,传统RECIST评估不能及时准确评价肿瘤治疗疗效。而影像学成像已进入功能化成像新时代,可提供微观分子及代谢改变信息。人工智能与放射影像组学通过挖掘图像背后更多的数学规律,可提供更多具有诊断价值的信息,有望为肺癌免疫治疗的疗效评价与预测提供新方法和新思路。本文就晚期肺癌免疫治疗的机制、现状及评价标准作一综述,重点分析影像学疗效评价与预测,并对其作出展望。     

Palliative immunotherapy of cancer

In addition to surgery, chemotherapy and radiation, immunotherapy of cancer resembles a potential treatment strategy for patients with cancer. To strengthen the immune system might help to control or even to eradicate malignant tumors. Immunoaugmentative strategies include biological response modifiers as interferons and interleukins. Recently, monoclonal antibodies directed against tumor associated antigens and coupled with radioisotopes or cytotoxic agents have become available. Adoptive immunotherapy uses immune effector cells, i.e. T-cells or natural-killer cells that are activated in-vitro by appropriate cytokines. Dendritic cells, either unstimulated or pulsed with tumor derived molecules have shown promising anticancer activity in selected tumors. Immunonutrition, that is the manipulation of immune phenomenons through edibles is a new and interesting topic. Immunologic strategies for the treatment of malignant diseases are currently under intensive preclinical and clinical investigation. Further insights into the mechanisms of host-defense against cancer cells and the modification of immune-effector cells might pave the way to efficient treatment strategies, even in the palliative setting.     

Immune monitoring of cancer patients undergoing experimental immunotherapy

Advancements in the understanding of cellular immunity within the last decade, along with the characterization of tumor antigens, have led to immunotherapeutic approaches for cancer therapy. This mode of treatment is expected to provide more tumor-specific activity, thereby being less toxic to normal cells than standard modalities. Clinical trials are underway throughout the world to determine whether immunotherapy is a practical and viable alternative to conventional cancer therapies. Unlike radiotherapy and chemotherapy, wherein tumor regression is the standard for determining efficacy of the regimens, immunotherapy has to be evaluated by the examination of several immunological parameters within patients. The purpose of this article is to review the methods currently utilized to evaluate the induction, maintenance, and duration of antitumor immune reactivity in cancer patients undergoing immunotherapy.