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
抗体与细胞因子联合治疗重编程 NK 细胞和巨噬细胞使肿瘤易于被检查点阻断清除
英文原题：Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade.
查看英文原题
Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade.
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中文摘要
旨在增强癌症免疫检查点阻断（ICB）疗效的治疗通常聚焦于T细胞免疫，但固有免疫细胞可能发挥重要作用。在此，我们展示了一种单剂量联合治疗方案（称为AIP），该方案使用泛肿瘤靶向抗体替代物、半衰期延长的白细胞介素-2（IL-2）和抗程序性细胞死亡1（PD-1），可使肿瘤对后续ICB治疗敏感，并促进小鼠体内已形成的大肿瘤消退。经AIP治疗激活的自然杀伤（NK）细胞和巨噬细胞发生了转录重编程；快速杀伤癌细胞；调控交叉呈递树突状细胞（DC）及其他白细胞的募集；并诱导肿瘤血管正常化，从而促进进一步的免疫浸润。因此，固有免疫细胞激活疗法可以启动关键步骤，导致由ICB驱动的T细胞致敏自我维持循环。
展开英文摘要原文
Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play.
Here, we demonstrate a single-dose combination treatment (termed AIP) using a pan-tumor-targeting antibody surrogate, half-life-extended interleukin-2 (IL-2), and anti-programmed cell death 1 (PD-1), which primes tumors to respond to subsequent ICB and promotes rejection of large established tumors in mice.
Natural killer (NK) cells and macrophages activated by AIP treatment underwent transcriptional reprogramming; rapidly killed cancer cells; governed the recruitment of cross-presenting dendritic cells (DCs) and other leukocytes; and induced normalization of the tumor vasculature, facilitating further immune infiltration.
Thus, innate cell-activating therapies can initiate critical steps leading to a self-sustaining cycle of T cell priming driven by ICB.
论文信息
- 作者
- Wang C、Cui A、Bukenya M、Aung A、Pradhan D、Whittaker CA、Agarwal Y、Thomas A
- 第一作者单位
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.United Kingdom
- 通讯作者单位
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: djirvine@mit.edu.United Kingdom
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Cell reports2021 Nov 23
- 原文标识
- PubMed 34818534 · DOI 10.1016/j.celrep.2021.110021
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