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 the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.
Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.
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尽管已有多种治疗选择,结直肠癌(CRC)仍然是癌症相关死亡率的重要因素。当前的标准治疗干预措施,包括手术、化疗以及免疫检查点阻断和抗血管生成治疗等靶向药物,已根据疾病分期改善了患者的短期结局,但转移患者的生存率仍然很低。一种有望改善CRC临床治疗体验的策略是使用树突状细胞(DC)疫苗,激发针对肿瘤源性血管的免疫反应,而肿瘤源性血管是CRC生长和进展所必需的。在本报告中,我们在结直肠癌同系小鼠模型中,使用临床相关的α1型极化DC疫苗(αDC1)靶向表达DLK1的肿瘤源性周细胞。我们的临床前数据表明,αDC1疫苗能够通过促进细胞毒性T淋巴细胞活性和消融肿瘤血管系统来诱导抗肿瘤效应。总体而言,这项工作为进一步探究免疫介导的保护机制奠定了基础,以帮助制定针对CRC患者的有效αDC1-based策略。
Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low.
A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer.
Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.
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