Documentdetail
ID kaart
doi:10.1038/s41419-024-06563-3...
Auteur
Li, Jinghan Shi, Daiwang Li, Siyi Shi, Xiang Liu, Yu Zhang, Yi Wang, Gebang Zhang, Chenlei Xia, Tian Piao, Hai-long Liu, Hong-XuLangue
enEditor
Nature
Categorie
Life Sciences
Jaar
2024
vermelding datum
28-02-2024
Trefwoorden
keap1 nsclc cancer pd-l1Beschrijving
Immunotherapy has become a prominent first-line cancer treatment strategy.
In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy.
However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer.
In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation.
We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo.
These results indicate the important role of KEAP1 in anti-cancer immunity.
Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation.
Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis.
In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling.
Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.
Li, Jinghan,Shi, Daiwang,Li, Siyi,Shi, Xiang,Liu, Yu,Zhang, Yi,Wang, Gebang,Zhang, Chenlei,Xia, Tian,Piao, Hai-long,Liu, Hong-Xu, 2024, KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC, Nature
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