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:Targeting innate and adaptive immunity to suppress lung cancer metastasis.
Targeting innate and adaptive immunity to suppress lung cancer metastasis.
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肺癌仍是全球癌症相关死亡的主要原因,转移和复发是预后不良的主要决定因素。尽管免疫治疗取得了进展,但免疫检查点抑制剂(ICIs)的原发性和获得性耐药凸显了探索替代免疫调节策略的必要性。新出现的证据强调了肿瘤微环境(TME)中固有免疫细胞和适应性免疫细胞在抑制或促进转移播散中的关键而双重的作用。以T细胞和B细胞为主的适应性免疫协调情境依赖性的抗肿瘤反应或免疫抑制,而固有免疫失调则促进转移龛的形成。我们重点介绍了转化机会,如自然杀伤(NK)细胞激活、巨噬细胞重编程和基于树突状细胞(DC)的疫苗,以及预后生物标志物如外周NK活性和类胰蛋白酶+肥大细胞浸润。本综述总结了免疫细胞亚群,包括T和B淋巴细胞、巨噬细胞、DCs、NK细胞和肥大细胞,在肺癌进展中的相互作用。通过综合临床前和临床研究见解,本综述指出了尚未解决的挑战,并提出靶向固有免疫作为增强当前疗法和减轻转移的有前景的途径。
Lung cancer remains the leading cause of cancer-related mortality globally, with metastasis and recurrence as the primary determinants of poor prognosis. Despite advances in immunotherapy, intrinsic and acquired resistance to immune checkpoint inhibitors (ICIs) underscores the need to explore alternative immunomodulatory strategies.
Emerging evidence highlights the critical yet dual roles of innate and adaptive immune cells within the tumor microenvironment (TME) in either restraining or facilitating metastatic dissemination. Adaptive immunity, dominated by T and B cells, orchestrates context-dependent antitumor responses or immunosuppression, while innate immune dysregulation fosters metastatic niches.
We highlight translational opportunities, such as natural killer (NK) cell activation, macrophage reprogramming, and dendritic cell (DC)-based vaccines, alongside prognostic biomarkers like peripheral NK activity and tryptase + mast cell infiltration.
This review summarizes the interplay of immune cell subsets, including T and B lymphocytes, macrophages, DCs, NK cells, and mast cells, in lung cancer progression. By synthesizing preclinical and clinical insights, this review identifies unresolved challenges and proposes targeting innate immunity as a promising avenue to augment current therapies and mitigate metastasis.
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