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:Killer instincts: natural killer cells as multifactorial cancer immunotherapy.
Killer instincts: natural killer cells as multifactorial cancer immunotherapy.
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自然杀伤(NK)细胞利用生殖系编码受体整合异质性的激活和抑制信号。这些受体以随机方式共表达,其同时结合和信号传导可调节单个细胞对潜在靶标的敏感性。癌症会在治疗和免疫压力下发生突变并演化,NK细胞提供的识别多样性可能是实现全面癌症控制的关键。NK细胞已用于过继细胞疗法临床试验,也已成为免疫治疗药物的靶点。然而,利用NK细胞天然多样性和灵活性的策略尚未开发出来。本综述讨论NK细胞产生激活或抑制信号的受体和信号通路,重点关注其在癌症中的作用及作为免疫治疗靶点的潜力。最后,我们探讨受体共表达的影响,以及同时激活多条NK细胞反应通路以最大化抗肿瘤作用范围和强度的可能性。
Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets.
Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents.
However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies.
Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.
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