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排序方式: 共有318条查询结果,搜索用时 15 毫秒
1.
Zhen Zeng Hui Yi Chew Jazmina G. Cruz Graham R. Leggatt James W. Wells 《International journal of molecular sciences》2021,22(6)
T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8+ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models. 相似文献
2.
Maria Buuales Maria Cristina Ballesteros-Briones Manuela Gonzalez-Aparicio Sandra Hervas-Stubbs Eva Martisova Uxua Mancheo Ana Ricobaraza Sara Lumbreras Cristian Smerdou Ruben Hernandez-Alcoceba 《International journal of molecular sciences》2021,22(8)
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer. 相似文献
3.
Vicen Ruiz de Porras Juan Carlos Pardo Lucia Notario Olatz Etxaniz Albert Font 《International journal of molecular sciences》2021,22(9)
Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC. 相似文献
4.
针对嵌入式Linux系统的特点,通过设置检查点(checkpoint)实现ARM平台进程级容错。在检查点工作时,通过/proc文件系统与内核进行交互,实时地获取与进程有关的PID、CPU状态以及内存信息,并保存在存储介质中。当进程出现故障后,将上述与进程有关的状态信息进行恢复,从而实现进程级容错。实验表明,该进程级容错系统有较好的容错能力,极大地缩短了进程恢复的时间。 相似文献
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6.
本文提出了在资源管理系统中基于作业检查点实现自动容错支持,深入分析了作业与任务检查点分离、映像文件管理、自动恢复执行等关键技术。基于BLCR在SLURM中实现了作业的自动检查点/恢复,详细介绍了实现中的关键技术难题。分析与测试表明,检查点与恢复执行功能正确,并能有效缩短大规模作业成功运行所需的时间。 相似文献
7.
Fan Gao Chi Zhang Wen‐Xiu Qiu Xue Dong Di‐Wei Zheng Wei Wu Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(37)
Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs‐mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD‐1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA‐Psi‐DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme‐activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP‐2. It is found that HA‐Psi‐DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon‐γ. This cytokine promotes the expression of programmed cell death protein‐ligand 1 (PD‐L1) on tumor cells, which will cause immunosuppression after interacting with PD‐1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA‐Psi‐DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti‐PD‐1 antibody (α‐PD1) due to the neutralization of immunosuppression by blocking the interaction between PD‐L1 and PD‐1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy. 相似文献
8.
9.
减少检查点开销的一种方法 总被引:1,自引:0,他引:1
设置检查点(checkpointing)是容错计算机系统进行故障恢复的重要手段。设置检查点的开销则是影响其性能的一个主要因素。文章提出了一种预先保存部分检查点数据的新方法。该方法不仅能够有效地减少检查点开销,而且具有比较短的检查点延迟。 相似文献
10.
For distributed databases, checkpointing is used to ensure an efficient way to perform global reconstruction. However, the need for global reconstruction is infrequent. Most current checkpointing approaches for distributed databases are too expensive during run time. Some of them allow the checkpointing process to run in parallel with normal transactions at the cost of more data and resource contention, which in turn causes longer response time for normal transactions. Thus, an efficient way to checkpoint distributed databases is needed to avoid degrading the system performance. This paper presents a low-cost solution, called Loosely Synchronized Local Fuzzy Checkpointing (LSLFC), to these problems. LSLFC supports global reconstruction, and our performance study shows that LSLFC has little overhead during run time. 相似文献