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:Cellular senescence in the innervated niche modulates cancer-associated pain: an emerging therapeutic target?
Cellular senescence in the innervated niche modulates cancer-associated pain: an emerging therapeutic target?
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癌细胞与神经系统之间的相互作用建立了所谓的“神经支配生态位”。肿瘤微环境(TME)的这一组成部分影响肿瘤进展,并以不同方式调控癌症相关疼痛的发生和维持。衰老是一种细胞应激反应,已成为癌症和衰老的标志。通过被称为衰老相关分泌表型(SASP)的炎性分泌组,衰老细胞执行免疫调节和组织重塑,参与许多生理病理过程。由于炎症是TME以及神经病变的关键决定因素,在这篇综述文章中,我们试图概述衰老在神经支配生态位中可能的作用。我们认为,衰老可通过增强TME中的局部炎症,促进神经炎症,而后者目前被认为既是癌症疼痛也是非癌症疼痛的初始触发因素。与此同时,衰老细胞可以成为神经支配生态位中可靶向的要素,以控制癌症疼痛。我们描述了免疫系统如何支持疼痛的缓解,并提出利用自然杀伤(NK)细胞——先天免疫淋巴细胞的原型——作为旨在缓解疼痛的治疗方法的可能性。
Crosstalk between cancer cells and the nervous system establishes the so-called "innervated niche". This component of the tumor microenvironment (TME) influences tumor progression and variably regulates the genesis and maintenance of cancer-related pain. Senescence is a cellular stress response emerging as a hallmark of cancer and aging.
Through the inflammatory secretome referred to as the senescence-associated secretory phenotype (SASP), senescent cells execute immunomodulation and tissue remodeling, participating in many physio-pathological processes. As inflammation is a key determinant of the TME as well as of neuropathies, in this review article we try to outline the possible role of senescence in the innervated niche.
We argue that senescence can contribute to neuroinflammation, which is nowadays recognized as the initial factor triggering both cancer and non-cancer pain, by boosting local inflammation in the TME. At the same time, senescent cells can become targetable elements of the innervated niche to control cancer pain.
We describe how the immune system supports the resolution of pain, and we suggest the possibility of harnessing natural killer (NK) cells, the prototype of innate immunity lymphocytes, for therapeutic approaches aimed at pain relief.
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