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以免疫检查点阻断疗法为代表的肿瘤免疫治疗在肿瘤临床治疗中取得了突破性进展,然而肿瘤免疫治疗伴随诊断仍存在诸多困难。在当前精准医疗大发展的背景下,创新性的技术和方法不断应用到肿瘤免疫治疗的伴随诊断中,对于提高肿瘤免疫治疗的效率具有重要意义。现有研究发现肿瘤微环境PD-L1的表达检测、肿瘤突变和肿瘤变异新抗原分析、肿瘤微环境免疫相关基因表达谱分析等方法与肿瘤免疫治疗效果具有显著相关性,然而其临床应用仍具有一定局限性,导致精准的肿瘤免疫治疗伴随诊断仍面临诸多挑战。主要介绍了免疫检查点阻断治疗相关伴随诊断领域研究进展,提出肿瘤免疫治疗伴随诊断需要开放式思维,积极引入新技术新方法,拓展多元化分子标识,从而推动肿瘤免疫治疗实现个体化精准应用。 相似文献
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肿瘤免疫治疗是继传统的手术、化疗、放疗之后的一种新兴的肿瘤治疗手段,因其具有特异性高、疗效显著等优点而备受学者们的关注。随着对肿瘤微环境和肿瘤逃逸机制的深入了解,调动机体免疫系统去抵御肿瘤逐渐成为一种新的研究方向。肿瘤免疫治疗主要包括特异性疗法和非特异性疗法,目前以肿瘤疫苗和单克隆抗体为代表的特异性免疫疗法在临床上得到广泛应用,并显示出良好的发展前景。但肿瘤免疫治疗仍存在认识不足、临床适应证有限等问题,与此同时,我国肿瘤免疫治疗的发展较国外仍相对不足且面临一些特殊的问题。本文将对目前已有的肿瘤免疫治疗方法及评价体系进行综述,并对一些新的技术手段和治疗思路展开讨论,此外还将结合国内外最新研究进展深入探讨这一新兴疗法的缺陷及未来的发展趋势。 相似文献
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肿瘤免疫治疗是通过调节机体的免疫功能来控制和杀伤肿瘤的一种治疗手段。针对免疫检查点的治疗等一系列临床突破使得肿瘤的免疫治疗受到了广泛重视。目前,抗体治疗和过继性细胞治疗是肿瘤免疫治疗的主要方式,但是这些方法仍具有副作用较强,实体瘤治疗难以实现,治疗费用高昂等缺点。因此改进和发展更加高效、安全、低成本的新技术仍十分必要。适配体是利用指数富集的配体系统进化技术筛选得到的单链寡核苷酸,有核酸"抗体"之称。适配体具有低免疫原性、组织穿透力强、易于化学合成与修饰等优势,且与其靶标的结合具有较好亲和力和特异性,可像抗体一样实现肿瘤的免疫治疗。对适配体在肿瘤免疫治疗相关技术中的新应用作一综述,主要包括基于免疫检查点的抗肿瘤作用、双特异性适配体的肿瘤免疫治疗、适配体靶向递送siRNA的肿瘤免疫治疗和适配体联合抗体的肿瘤免疫治疗等方面。 相似文献
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Brachyury是T-box转录因子家族的重要成员,与肿瘤发展密切相关,在肿瘤上皮-间质转化(epithelial-mesenchymal transition,EMT)中发挥重要作用,可能成为肿瘤免疫治疗的潜在靶点。从Brachyury与肿瘤转移、分期、预后的关系,对肿瘤EMT的诱导调节,对肿瘤传统治疗的抵抗及靶向Brachyury的肿瘤免疫治疗等方面进行了综述,并展望了Brachyury未来的研究方向和临床应用前景。 相似文献
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近年来,肿瘤免疫治疗(cancer immunotherapies)已成为晚期恶性肿瘤治疗的重要手段之一。肿瘤免疫治疗并不直接攻击癌细胞,而是通过调节人体自身免疫系统来抗击肿瘤,有望像抗生素改变抗感染治疗一样改变肿瘤治疗范式。抗PD-1/L1和抗CTLA-4抗体药物作为肿瘤免疫治疗的代表药物,使晚期癌症患者五年生存率达成了数倍的提升,被认为是真正有希望治愈癌症的治疗方式。然而,肿瘤免疫治疗只对部分患者有效,并且存在耐药、超进展、不良反应等问题。如何准确筛选出最有可能从治疗中获益的人群成为肿瘤免疫治疗研究中的一个重大挑战。目前有多个与免疫治疗相关的生物标志物正在研究中,并且有望被用于临床筛选治疗获益人群;但这些生物标记物也存在很多缺陷。未来,围绕免疫治疗敏感性和副反应的多项指标综合评估可能成为一个趋势。 相似文献
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肿瘤免疫治疗已成为各种原发性和转移性癌症的有效治疗方式。纳米药物递送系统(nano drug delivery system, NDDS)具有生物利用度高、靶向性好的优点,在肿瘤靶向治疗和免疫治疗等方面受到广泛关注。然而,传统的NDDS在临床应用中存在易被免疫系统识别和清除、跨越生物屏障能力差等问题。仿生药物递送系统(biomimetic drug delivery system, BDDS)以其良好的生物相容性和较低的免疫原性成为新一代极具前景的治疗策略。哺乳动物的细胞(如红细胞、血小板、单核细胞、巨噬细胞、中性粒细胞和T淋巴细胞等)及其细胞膜源于母体生物系统,具有独特的生物学特征,成为研究的热点。该文综述了近年来基于细胞膜和细胞的BDDS在改善肿瘤免疫治疗中的最新进展,重点介绍了这些BDDS的构建方式、表征手段和应用研究,并对其在改善肿瘤免疫治疗效果领域面临的挑战及未来的发展进行了讨论。 相似文献
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Ren Guanghui Hao Xiaoyan Yang Shuyi Chen Jun Qiu Guobin 《Journal of biochemical and molecular toxicology》2019,33(8)
Breast cancer (BC) is one of the most widespread malignancies in women worldwide. Breast cancer is mainly classified into a few key molecular subtypes in accordance with hormone and growth factor receptor expression, etc. In spite of numerous advances in the remedy of breast cancer, the development of metastatic disease remains an untreatable and repeated basis of cancer death for women. Preclinical and clinical studies of immunotherapy in cancer remedy have been in progress for the past quite a few decades by an effort to accelerate, augment, and modulate the immune system to spot and devastate cancer cells. Advancement of cancer immunotherapy is rapidly increasing with eminent and most interesting therapy compared to other therapy like targeted therapy, cytotoxic chemotherapy, radiation as well as surgery. Cancer immunotherapy, also known as biological therapy, which denotes the controlling and by means of the patient's own immune system to goal the cancer cells rather than using an extrinsic therapy. In that way, focusing of cancer immunotherapy developing mediators that stimulates or enhances the immune system's recognition and destroying the cancer cells. This review describes a holistic outlook and deeper understanding of the biology of immunotherapy within the system of tumor microenvironment of breast cancer that improve clinical research and constructive impact on the study conclusion. 相似文献
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《Cytokine & growth factor reviews》2014,25(4):377-390
The use of cytokines from the IL-2 family (also called the common γ chain cytokine family) such as interleukin (IL)-2, IL-7, IL-15, and IL-21 to activate the immune system of cancer patients is one of the most important areas of current cancer immunotherapy research. The infusion of IL-2 at low or high doses for multiple cycles in patients with metastatic melanoma and renal cell carcinoma was the first successful immunotherapy for cancer proving that the immune system could completely eradicate tumor cells under certain conditions. The initial clinical success observed in some IL-2-treated patients encouraged further efforts focused on developing and improving the application of other IL-2 family cytokines (IL-4, IL-7, IL-9, IL-15, and IL-21) that have unique biological effects playing important roles in the development, proliferation, and function of specific subsets of lymphocytes at different stages of differentiation with some overlapping effects with IL-2. IL-7, IL-15, and IL-21, as well as mutant forms or variants of IL-2, are now also being actively pursued in the clinic with some measured early successes. In this review, we summarize the current knowledge on the biology of the IL-2 cytokine family focusing on IL-2, IL-15 and IL-21. We discuss the similarities and differences between the signaling pathways mediated by these cytokines and their immunomodulatory effects on different subsets of immune cells. Current clinical application of IL-2, IL-15 and IL-21 either as single agents or in combination with other biological agents and the limitation and potential drawbacks of these cytokines for cancer immunotherapy are also described. Lastly, we discuss the future direction of research on these cytokines, such as the development of new cytokine mutants and variants for improving cytokine-based immunotherapy through differential binding to specific receptor subunits. 相似文献
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Xue Bin Xu Jiaqi Song Wenru Yang Zhimin Liu Ke Li Zihai Li Zihai Chen Lieping Garon Edward B. Hu-Lieskovan Siwen Ding Wei Pan Chong-Xian Sun Weijing Liu Yong-Jun Zheng Lei Liu Delong Sadelain Michel Yee Cassian Wang Rongfu Chen Meixia Wang Yao Wu Zhiqiang Dai Hanren Luo Can Liu Yang Tong Chuan Guo Yelei Yang Qingming Han Weidong Butterfield Lisa H. Chan Timothy A. Song Wenru Yuan Ruirong Lu Bo Liu Ke Ning Max Enzmann Harald Zwierzina Heinz 《Journal of hematology & oncology》2016,9(1):1-10
A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina 相似文献
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Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+ T cells 总被引:3,自引:0,他引:3
Matsumoto S Saito H Tsujitani S Ikeguchi M 《Cancer immunology, immunotherapy : CII》2006,55(2):131-139
The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential
use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic.
However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell–DC hybrids were used
to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer
cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen
(TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting
in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4+ T cells
proliferation. CD8+ T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization.
The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition
of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing
is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell–DC
hybrids in DC based immunotherapy for gastric cancer treatment. 相似文献
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美国免疫学家詹姆斯·艾利森(James P.Allison)与日本免疫学家本庶佑(Tasuku Honjo)因在免疫检查点治疗方面的贡献而获得了2018年诺贝尔生理学或医学奖.这一发现为免疫治疗开启了一扇新的大门.本文回顾了免疫检查点CTLA-4和PD-1的研究历史,免疫检查点药物的研发和应用进展以及免疫检查点疗法在国内的发展现况,提出了免疫检查疗法目前存在的局限性和解决方法.随着近年来我国在免疫治疗领域巨大的资金投入、一流基础研究平台的建设和优秀人才的回国使得我国在这一领域硕果累累,相信在不久的将来我国的免疫检查点抑制剂将会走出国门,为全人类的癌症事业做出贡献. 相似文献
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Ferrantini M Capone I Marincola FM Parmiani G Belardelli F 《Cancer immunology, immunotherapy : CII》2007,56(4):581-585
The main aims of the international meeting “Immunotherapy of Cancer: Challenges and Needs” were to review the state of the
art of cancer immunotherapy and to identify critical issues which deserve special attention for promoting progress of research
in this field, with a particular focus on the perspectives of clinical research. Novel concepts and strategies for identifying,
monitoring and predicting effective responses to cancer immunotherapy protocols were presented, focused on the use of adjuvants
(CpG oligonucleotides) or cytokines (IFN-alpha) to enhance the efficacy of cancer vaccines. Moreover, the possible advantages
of using different types of dendritic cells (for active immunization strategies) or T cells (for adoptive immunotherapy protocols)
were debated. A consensus was achieved on the need for enhancing the efficacy of cancer vaccines or adoptive cell immunotherapy by combining these
strategies with other anti-cancer treatments, including chemotherapy. Finally, initiatives for promoting clinical research
by establishing a strategic cooperation in the field of cancer immunotherapy based on the active participation of all the
relevant actors, including public institutions responsible of Public Health, National Cancer Institutes, industry, representatives
of regulatory bodies, and patients’ organizations were proposed. 相似文献
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肝细胞肝癌是全球发病率和死亡率最高的恶性肿瘤之一,发病率和死亡率呈逐年上升趋势。我国是肝癌大国,每年肝癌的死亡病例数位居全球第一。免疫治疗是继手术、化疗和放疗之后新兴的癌症治疗手段,其通过解除肿瘤微环境对免疫细胞的抑制作用并激活机体免疫功能,实现控制和杀伤肿瘤细胞。常用的免疫治疗的方法有免疫检查点治疗、过继免疫治疗和肿瘤疫苗治疗等。与传统治疗手段相比,免疫治疗因具有增强机体免疫功能、延缓肿瘤进展、延长患者生存时间等优点,逐渐成为基础和临床研究的热点。文中就免疫治疗在肝癌领域的研究进展作一综述。 相似文献
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《生物化学与生物物理学报:癌评论》2023,1878(1):188848
Exploring effective systemic treatments for liver cancer is still a great challenge worldwide. As a novel form of regulated cell death, ferroptosis has been paid more and more attention in the cancer research field. In recent years, targeting ferroptosis has become an encouraging strategy for liver cancer treatment. Cancer cells can be directly killed by inducing ferroptosis; in contrast, ferroptosis can also ameliorate the tumor immunosuppressive microenvironment and sensitize cancers to immunotherapy. Here, we summarize fully current progress in the iron homeostasis in the liver, the internal association between imbalanced iron homeostasis and ferroptosis in liver carcinogenesis and development, as well as ferroptosis-related regulators in liver cancer. Furthermore, we discuss thoroughly the interaction between ferroptosis and tumor immune microenvironment. Finally, we provide certainly a future insight on the potential value of ferroptosis in the immunotherapy of liver cancer. 相似文献
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History of cancer immunotherapy lasts for more than 120 years. In 1891 William B. Coley injected bacteria into inoperable cancer (bone sarcoma) and observed tumor shrinkage. He is recognized as the "'"Father of Immunotherapy"'". Cancer immunotherapy is based on the ability of the immune system to recognize cancer cells and to affect their growth and expansion. Beside the fact that, tumor cells are genetically distinct from their normal counterparts, and should be recognized and eliminated by immune system, the tumor associated antigens (TAAs) are often poorly immunogenic due to immunoediting. This process allows tumor to evolve during continuous interactions with the host immune system, and eventually escape from immune surveillance. Furthermore, tumor microenvironment consists of immunosuppressive cells that release immunosuppressive factors including IL-6, IL-10, IDO, TGFβ or VEGF. Interactions between cancer and stroma cells create network of immunosuppressive pathways, while activation of immune defense is inhibited. A key to successful immunotherapy is to overcome the local immunosuppression within tumor microenvironment and activate mechanisms that lead to tumor eradication. There are two clinical approaches of immunotherapy: active and passive. Active immunotherapy involves stimulation of immune response to tumor associated antigens (TAAs), either non-specifically via immunomodulating agents or specifically employing cancer vaccines. This review presents the progress and breakthroughs in design, development and clinical application of selected cell-based tumor vaccines achieved due to the generation and development of gene transfer technologies. 相似文献