研究动态
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铂基双药物调节肿瘤浸润免疫细胞,提高免疫检查点阻断治疗的效果。

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

发表日期:2023 Sep 20
作者: Yuhao Hao, Rui Li, Yuanzeng Min
来源: Cell Death & Disease

摘要:

化学免疫疗法是一个正在积极研究和发展的领域,越来越多的证据支持其在癌症治疗中的潜在益处。然而,化疗组分在化学免疫疗法中存在一些局限性,包括全身毒性和在逆转免疫抑制的肿瘤微环境方面表现不佳。在这里,我们设计了一个双药物MROP,与全反式视黄酸和奥沙利铂结合,并表明双药物显著增强了与抗PD-1联合治疗在结直肠癌小鼠模型中的协同治疗效果。通过对肿瘤组织的机制分析,我们证明了抗PD-1和MROP的组合诱导了免疫原性细胞死亡,并调节了肿瘤浸润的免疫细胞,包括将肿瘤相关巨噬细胞极化为1型、减少髓系抑制细胞的数量,并显著增加了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希望的策略,并对化学免疫疗法的机制提供了新的见解。
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.