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:Pt-Te-Nanorod-Based Photothermal Chemokine Immunotherapy for All Stages of Cancer via Adaptive and Innate Immunity.
Pt-Te-Nanorod-Based Photothermal Chemokine Immunotherapy for All Stages of Cancer via Adaptive and Innate Immunity.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
趋化因子(C-X-C基序)配体9(CXCL9)是参与淋巴细胞运输的趋化因子之一。尽管CXCL9具有将效应T细胞(分化簇4+(CD4+)和CD8+ T细胞)和NK 细胞(NK细胞)募集到肿瘤周围的免疫治疗潜力,但由于其免疫毒性和在体内缺乏稳定性,CXCL9的实际应用受到限制。为克服这些局限性,我们设计并合成了Pt-Te纳米棒(PtTeNRs),其在体内环境的生理条件下表现出优异的光热转换效率和稳定的CXCL9负载特性。
我们利用所开发的PtTeNRs独特的理化性质,开发了一种基于CXCL9的免疫治疗策略。研究表明,负载PtTeNR的CXCL9有效蓄积于肿瘤中,随后以持续方式释放,并成功募集效应T细胞对指定肿瘤组织进行免疫治疗。
此外,还观察到光热(PT)治疗与抗程序性细胞死亡蛋白1(aPD-1)抗体之间的协同效应。在本研究中,我们证明了基于PtTeNR的CXCL9、PT和aPD-1抗体三联疗法在癌症的所有阶段(包括1-4期和肿瘤复发)均具有出色的肿瘤抑制效果。
The chemokine (C-X-C) motif ligand 9 (CXCL9) is one of the lymphocyte-traffic-involved chemokines. Despite the immunotherapeutic potential of CXCL9 for recruiting effector T cells (cluster of differentiation 4 + (CD4 + ) and CD8 + T cells) and natural killer cells (NK cells) around the tumors, practical applications of CXCL9 have been limited because of its immune toxicity and lack of stability in vivo.
To overcome these limitations, we designed and synthesized Pt-Te nanorods (PtTeNRs), which exhibited excellent photothermal conversion efficiency with stable CXCL9 payload characteristics under the physiological conditions of in vivo environments.
We developed a CXCL9-based immunotherapy strategy by utilizing the unique physicochemical properties of developed PtTeNRs. The investigation revealed that the PtTeNR-loaded CXCL9 was effectively accumulated in the tumor, subsequently released in a sustained manner, and successfully recruited effector T cells for immunotherapy of the designated tumor tissue.
In addition, a synergistic effect was observed between the photothermal (PT) therapy and antiprogrammed cell death protein 1 (aPD-1) antibody. In this study, we demonstrated that PtTeNR-based CXCL9, PT, and aPD-1 antibody trimodal therapy delivers an outstanding tumor suppression effect in all stages of cancer, including phases 1-4 and tumor recurrence.
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