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靶向周细胞抗原 DLK1 的α1 型极化树突状细胞疫苗可导致肿瘤血管调节并防止结肠癌进展

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.

查看英文原题

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.

PubMed 2023/10/02(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
McCormick AL、Anderson TS、Daugherity EA、Okpalanwaka IF、Smith SL、Appiah D、Lowe DB
单位
Department of Immunotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, United States.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究 · 美国政府(非公共卫生署)资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 37849752 · DOI 10.3389/fimmu.2023.1241949