一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Proceedings of the National Academy of Sciences of the United States of America >>article

QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion

Published:29 October 2024 DOI: 10.1073/pnas.2407506121 PMID: 39432781
Jia-Ru Wei,?Baifeng Zhang,?Yu Zhang,?Wo-Ming Chen,?Xiao-Ping Zhang,?Ting-Ting Zeng,?Yan Li,?Ying-Hui Zhu,?Xin-Yuan Guan,?Lei Li

Abstract

Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk+ CD8+ T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD-L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast-derived quiescin sulfhydryl oxidase 1 (QSOX1) promotes the expression of PD-L1 and its own expression in DCSCs by elevating the level of reactive oxygen species. Additionally, high QSOX1 in the dormant tumor niche contributes to the exclusion of CD8+ T cells. Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8+ T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ebselen 60940-34-3 C13H9NOSe 289 suppliers $12.00-$3437.00
Ebselen 60940-34-3 C13H9NOSe 289 suppliers $12.00-$3437.00
Ebselen 60940-34-3 C13H9NOSe 289 suppliers $12.00-$3437.00
Ebselen 60940-34-3 C13H9NOSe 289 suppliers $12.00-$3437.00
微山县| 永城市| 金溪县| 灌南县| 平远县| 永福县| 云安县| 浮山县| 钦州市| 丰县| 额尔古纳市| 南宫市| 五家渠市| 瓮安县| 博兴县| 富平县| 卓资县| 高州市| 洛浦县| 聂荣县| 咸宁市| 鹰潭市| 吉水县| 项城市| 垫江县| 永兴县| 沅江市| 离岛区| 泸溪县| 杭锦后旗| 金坛市| 阜新| 巩留县| 阳山县| 囊谦县| 清镇市| 廉江市| 塔城市| 赣榆县| 南阳市| 称多县|