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.
肿瘤细胞治疗研究
英文原题:The role of the natural killer (NK) cell modulation in breast cancer incidence and progress.
The role of the natural killer (NK) cell modulation in breast cancer incidence and progress.
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多年来,研究人员一直在探讨免疫系统在肿瘤监视中的重要性,其控制肿瘤进展的作用也已得到证实。自然杀伤(NK)细胞是先天免疫系统的重要亚群,其调节肿瘤行为、抑制转移和肿瘤生长的关键作用已得到证明。NK细胞生物学功能的重要线索,最初来自其强大的直接细胞毒能力,而且这种作用无需预先致敏。凭借这些特性,NK细胞能够识别自身配体表达减少、同时表达应激诱导配体的转化细胞。此外,NK细胞活化后会分泌多种细胞因子和趋化因子,既可直接杀伤恶性细胞,也可激活适应性免疫系统,从而清除肿瘤。新型免疫治疗也在利用NK细胞的这些能力,包括基于抗体的疗法、工程化CAR-NK细胞以及过继细胞转移。然而,NK细胞功能受限、难以浸润肿瘤,仍是其用于乳腺癌患者治疗时的短板。本文汇总了NK细胞在乳腺癌中的生物学和功能研究新进展,并探讨如何将这些认识转化为癌症、尤其是乳腺癌的新治疗策略。
The importance of the immune system on tumor surveillance has been investigated for many years, and its impact on controlling tumor progression has been verified. An important subgroup of the innate immune system is natural killer (NK) cells, whose essential function in modulating tumor behavior and suppressing metastasis and tumor growth has been demonstrated.
The first idea of NK cells' crucial biological processes was demonstrated through their potent ability to conduct direct cellular cytotoxicity, even without former sensitization. These properties of NK cells allow them to recognize transformed cells that have attenuated self-ligand and express stress-induced ligands.
Furthermore, secretion of various cytokines and chemokines after their activation leads to tumor elimination via either direct cytotoxic effect on malignant cells or activation of the adaptive immune system.
In addition, novel immunotherapeutic approaches tend to take advantage of NK cells' ability, leading to antibody-based approaches, the formation of engineered CAR-NK cells, and adoptive cell transfer.
However, the restricted functionality of NK cells and the inability to infiltrate tumors are its blind spots in breast cancer patients. In this review, we gathered newly acquired data on the biology and functions of NK cells in breast cancer and proposed ways to employ this knowledge for novel therapeutic approaches in cancers, particularly breast cancer.
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