RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities.
Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities.
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迄今免疫治疗研究主要聚焦T细胞,但越来越多证据表明,肿瘤浸润B细胞和浆细胞(统称肿瘤浸润B淋巴细胞,TIL-B)在肿瘤控制中发挥关键的协同作用。在多种癌症中,无论标准治疗还是免疫检查点阻断背景下,TIL-B均显示出很强的预测和预后意义,为利用其独特免疫学特性开辟了新的治疗机会。本文借鉴自身免疫研究成果,综述人类癌症中TIL-B相关的分子表型、组织结构背景、抗原特异性、效应机制和调控通路。尽管该领域仍处早期,现有图景显示,TIL-B可通过其独特的抗原呈递方式促进抗肿瘤免疫;参与组建并维持涉及T细胞、髓系细胞和NK 细胞的“热”肿瘤微环境;并可能通过缓解自身耐受机制,对抗免疫编辑和肿瘤异质性。最后,本文讨论最有希望的策略,以协同其他免疫细胞亚群增强TIL-B应答,扩展癌症免疫治疗的适用范围、效力和持久性。
Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role in tumour control. In many cancers, TIL-Bs have demonstrated strong predictive and prognostic significance in the context of both standard treatments and immune checkpoint blockade, offering the prospect of new therapeutic opportunities that leverage their unique immunological properties.
Drawing insights from autoimmunity, we review the molecular phenotypes, architectural contexts, antigen specificities, effector mechanisms and regulatory pathways relevant to TIL-Bs in human cancer.
Although the field is young, the emerging picture is that TIL-Bs promote antitumour immunity through their unique mode of antigen presentation to T cells; their role in assembling and perpetuating immunologically 'hot' tumour microenvironments involving T cells, myeloid cells and natural killer cells; and their potential to combat immune editing and tumour heterogeneity through the easing of self-tolerance mechanisms.
We end by discussing the most promising approaches to enhance TIL-B responses in concert with other immune cell subsets to extend the reach, potency and durability of cancer immunotherapy.
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