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:Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?
Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?
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细胞毒性淋巴细胞(CLs),特别是细胞毒性T淋巴细胞和NK 细胞,是免疫系统不可或缺的守护者,协调对癌细胞的识别和清除。当遇到癌细胞时,CLs会建立一个专门的细胞连接,称为免疫突触,这是有效杀伤细胞的关键决定因素。大量研究集中在免疫突触的突触前侧,阐明了CL肌动蛋白细胞骨架在突触形成、组织、调节信号和裂解活性中的多种功能。相比之下,突触后(癌细胞)对应部分相对未被充分探索。
然而,间接和直接证据已开始揭示癌细胞内部细胞骨架变化对裂解性免疫突触结果的显著而深远的影响。在此,我们探讨癌细胞肌动蛋白细胞骨架在调节免疫突触内免疫反应中未被充分研究的角色。
我们阐明肌动蛋白动力学与癌细胞所采用的免疫逃逸机制之间的复杂相互作用,从而为未来研究提供潜在途径,并展望在癌症免疫治疗领域针对免疫突触突触后侧的治疗干预。这篇综述文章强调了细胞毒性淋巴细胞与癌细胞之间免疫突触内肌动蛋白动力学的重要性,重点关注突触中较少被探索的突触后侧。它呈现了新出现的证据,表明癌细胞中的肌动蛋白动力学可以关键性地影响细胞毒性淋巴细胞与癌细胞相互作用的结果。
Cytotoxic lymphocytes (CLs), specifically cytotoxic T lymphocytes and natural killer cells, are indispensable guardians of the immune system and orchestrate the recognition and elimination of cancer cells. Upon encountering a cancer cell, CLs establish a specialized cellular junction, known as the immunological synapse that stands as a pivotal determinant for effective cell killing.
Extensive research has focused on the presynaptic side of the immunological synapse and elucidated the multiple functions of the CL actin cytoskeleton in synapse formation, organization, regulatory signaling, and lytic activity. In contrast, the postsynaptic (cancer cell) counterpart has remained relatively unexplored. Nevertheless, both indirect and direct evidence has begun to illuminate the significant and profound consequences of cytoskeletal changes within cancer cells on the outcome of the lytic immunological synapse.
Here, we explore the understudied role of the cancer cell actin cytoskeleton in modulating the immune response within the immunological synapse.
We shed light on the intricate interplay between actin dynamics and the evasion mechanisms employed by cancer cells, thus providing potential routes for future research and envisioning therapeutic interventions targeting the postsynaptic side of the immunological synapse in the realm of cancer immunotherapy.
This review article highlights the importance of actin dynamics within the immunological synapse between cytotoxic lymphocytes and cancer cells focusing on the less-explored postsynaptic side of the synapse. It presents emerging evidence that actin dynamics in cancer cells can critically influence the outcome of cytotoxic lymphocyte interactions with cancer cells.
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