← 返回

基于铂的双药调节肿瘤浸润免疫细胞以改善免疫检查点阻断治疗

英文原题:Platinum-Based Twin Drug Modulates Tumor-Infiltrating Immune Cells to Improve Immune Checkpoint Blockade Therapy.

查看英文原题

Platinum-Based Twin Drug Modulates Tumor-Infiltrating Immune Cells to Improve Immune Checkpoint Blockade Therapy.

PubMed 2023/09/20(内容时间) J Med Chem Q1 · IF 7.3(JCR 2025)

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。

中文摘要

化学免疫治疗是一个活跃的研究和开发领域,越来越多的证据支持其在癌症治疗中的潜在益处。然而,化学免疫治疗中的化疗成分存在若干局限性,包括全身毒性以及在逆转免疫抑制性肿瘤微环境方面效果不佳。在此,我们设计了一种双药MROP,由全反式维甲酸和奥沙利铂复合而成,并表明该双药在结直肠癌小鼠模型中显著增强了与anti-PD-1的协同治疗效果。我们通过对肿瘤组织的机制分析证明,anti-PD-1与MROP联合可诱导免疫原性细胞死亡并调节肿瘤浸润免疫细胞,包括促使肿瘤相关巨噬细胞向1型极化、减少髓源性抑制细胞,以及显著增加T细胞比例,尤其是CD8 + T细胞。本文为癌症治疗提供了一种有前景的策略,并为化学免疫治疗的机制提供了新的见解。

展开英文摘要原文

Chemoimmunotherapy is an area of active research and development with a growing body of evidence supporting its potential benefits for the treatment of cancer.

However, chemotherapy components of chemoimmunotherapy have several limitations, including systemic toxicity and poor performance in reversing the immunosuppressive tumor microenvironment.

Here, we designed a twin drug, MROP, complexed with all-trans retinoic acid and oxaliplatin, and showed that the twin drug significantly enhanced the synergetic therapeutic efficacy with anti-PD-1 in a colorectal cancer mouse model.

We demonstrated by mechanistic analyses of tumor tissue that the combination of anti-PD-1 and MROP induced immunogenic cell death and regulated tumor-infiltrating immune cells, including the polarization of tumor-associated macrophages toward type 1, a reduction in myeloid-derived suppressor cells, and a significant increase in the proportion of T cells, particularly CD8 + T cells. This paper provides a promising strategy for cancer treatment and new insight into the mechanism of chemoimmunotherapy.

论文信息

作者
Hao Y、Li R、Min Y
单位
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.China
文献类型
非美国政府资助研究
期刊
Journal of medicinal chemistry2023 Oct 12
原文标识
PubMed 37728887 · DOI 10.1021/acs.jmedchem.3c00946