癌症研究
免疫疗法
结直肠癌
脱氮酶
癌症免疫疗法
癌症
医学
药理学
化学
内科学
生物化学
泛素
基因
作者
Jingjing Wu,Chang Liu,Tao Wang,Hua Liu,Bin Wei
出处
期刊:Immunology
[Wiley]
日期:2023-08-01
卷期号:170 (3): 439-451
被引量:3
摘要
A substantial number of colon cancer patients do not benefit from immunotherapy using programmed cell death 1 (PD1) antibodies. Therefore, combination therapy drugs are required to improve the efficacy of colon cancer immunotherapy. Recent studies have shown that deubiquitinases are negative regulators of anti-tumour immunity. In the present study, we investigated the effect of the deubiquitinase inhibitor PR-619 in combination with anti-PD1 for the treatment of colorectal cancer. The results revealed that co-treatment with PR-619 and anti-PD1 significantly inhibited tumour growth in tumour-bearing BALB/c mice compared to monotherapy with a single drug. In addition, PR-619/anti-PD1 combined therapy inhibited cell proliferation, promoted cell apoptosis, induced intratumor infiltration of CD8+ T cells, and enhanced the release of anti-tumour cytokines. Moreover, PR-619 induced ferroptosis in colon cancer cells, thereby inducing the release of damage-associated molecular patterns that triggered anti-tumour immunity. Finally, we discovered that PR-619 could degrade the GPX4 protein, the high expression of which was associated with poor prognosis and blocked CD8+ T cells infiltration in colon cancer. In conclusion, PR-619 may potentiate immunotherapy by inducing ferroptosis, and thereby promoting CD8+ T cells-mediated anti-tumour immunity, providing a potential strategy for colon cancer treatment.
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