Dataset Information

ARIH1 Signaling Promotes Anti-tumor Immunity by Targeting PD-L1 for Proteasomal Degradation

ABSTRACT: We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hongguang Xia

PROVIDER: PXD024452 | iProX | Mon Mar 01 00:00:00 GMT 2021

REPOSITORIES: iProX

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ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.

Wu Youqian Y Zhang Chao C Liu Xiaolan X He Zhengfu Z Shan Bing B Zeng Qingxin Q Zhao Qingwei Q Zhu Huaying H Liao Hongwei H Cen Xufeng X Xu Xiaoyan X Zhang Mengmeng M Hou Tingjun T Wang Zhe Z Yan Huanhuan H Yang Shuying S Sun Yaqin Y Chen Yanying Y Wu Ronghai R Xie Tingxue T Chen Wei W Najafov Ayaz A Ying Songmin S Xia Hongguang H

Nature communications 20210420 1

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 ...[more]

PMID: 33879767

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Project description:Purpose: To find out the patients who are most sensitive and effective to the anti-PD-L1 and TGF-β bifunctional fusion protein in the treatment of recurrent cervical cancer. Patients and methods: We report two cases of recurrent cervical cancer treated with the anti-PD-L1 and TGF-β bifunctional fusion protein. We described the clinical course, clinical characteristics, and genetic characteristics of the two patients, and analyzed the changes of gene expression in the two patients after treatment. Results: Although PD-L1 expression and HPV status were same in the two patients, the treatment effect of two patients with recurrent cervical cancer was different, according to the evaluation of enhanced computed tomography (CT), one was partial response (PR) and the other was progressive disease (PD), which may indicate that PD-L1 expression and HPV status of patients is not enough to predict the effectiveness of the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Then, we demonstrated that the changes of peripheral blood lymphocytes of two patients during the treatment had different trends. Moreover, number of alterable genes in PR patient is much greater than that in PD patient, indicating PR patient may be more sensible to the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Total 4844 genes changing-fate gene set selected which is believed conducting anti-cancer function during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Furthermore, we identified that changing-fate genes were correlated with female reproductive organ cancer, infectious disease, inflammatory disease, immune system, indicating these genes may conducting anti-cancer, anti-inflammation and immune function. Conclusion: Anti-PD-L1 and TGF-β bifunctional fusion protein is feasible for the treatment of recurrent cervical cancer. Multi-center, large-sample prospective clinical studies are still needed to further explore the efficacy of anti-PD-L1 and TGF-β bifunctional fusion protein in recurrent cervical cancer and screen appropriate patients, so as to achieve the maximum survival benefit of patients.

Dataset Information

ARIH1 Signaling Promotes Anti-tumor Immunity by Targeting PD-L1 for Proteasomal Degradation

Publications

ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.

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