Evidence map›Paper›PMID 42442361›Full record

ArticleCell reports. Medicine2026

Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.

Xuwen Lin, Qun Wang, Mengting Xu, Dianping Yu, Hongmei Hu, Qing Zhang, Jiannan Yao, Mei Xie, Hanchi Xu, Xuefeng Zang and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Xuwen LinDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
Qun WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Mengting XuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Dianping YuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Hongmei HuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Qing ZhangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Jiannan YaoBeijing Chao-Yang Hospital Department of Oncology, Capital Medical University, Beijing 100006, China.
Mei XieDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
Hanchi XuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Xuefeng ZangDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
Jia LiDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
Yu ChenDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China.
Linyang LiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Xiaoyu TaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Xinru LiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Simeng LiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China.
Shize XieDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Yating TianDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Weidong ZhangDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: wdzhangy@hotmail.com.
Sanhong LiuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai 201203, China. Electronic address: liush@shutcm.edu.cn.
Xinying XueDepartment of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China; Department of Respiratory and Critical Care, Shandong Second Medical University, Weifang 261053, China. Electronic address: xuexinying@xwhosp.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the clinical efficacy of PD-1/PD-L1 blockade in solid tumors, resistance mediated by PD-L1 protein stabilization necessitates alternative strategies. Our study identifies ethoxzolamide (EZA), a carbonic anhydrase inhibitor, as a negative regulator of PD-L1. EZA binds to the Leu387 residue of the E3 ubiquitin ligase β-TrCP, triggering K48-linked polyubiquitination and proteasomal degradation of PD-L1. Functionally, EZA downregulates tumor cell PD-L1, restoring T cell-mediated cytotoxicity in vitro. In Lewis lung carcinoma and MC38 murine models, EZA reprograms the tumor immune microenvironment (reducing MDSC/Treg infiltration while bolstering cytotoxic response). EZA synergizes with anti-CTLA-4 therapy to overcome treatment resistance. Clinical analysis of a neoadjuvant immunotherapy cohort of non-small cell lung cancer (NSCLC) patients reveals that high PD-L1 with low β-TrCP expression associates with superior response, suggesting that this axis may warrant further investigation. Our findings elucidate an antitumor mechanism of EZA and expand its therapeutic potential.

Indexed as

B7-H1 Antigenbeta-Transducin Repeat-Containing ProteinsUbiquitinationAnimalsCarcinoma, Lewis LungCarcinoma, Non-Small-Cell LungCell Line, TumorFemaleHumansLung NeoplasmsMiceMice, Inbred C57BLTumor MicroenvironmentB7-H1 Antigenbeta-Transducin Repeat-Containing ProteinsCD274 protein, humancancer immunotherapyethoxzolamideprogrammed death-ligand 1ubiquitination and degradationβ-transducin repeat-containing protein

Identifiers

PMID42442361
PMCPMC13400190

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.