Evidence map›Paper›PMID 40514069›Full record

ArticleJournal for immunotherapy of cancer2025

ADRB2 inhibition suppresses cancer immune evasion by regulating tumor SOX10-PD-L1 axis and T cell function.

Yu Zhang, Feng Yu, Jing Ouyang, Panpan Liu, Yingying Dai, Yang Wang, Hanying Yi, Shiyu Wang, Dongbo Liu, Kun Song and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

20 authors.

Yu Zhang *Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Feng Yu *Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Jing Ouyang *Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Panpan LiuDepartment of Dermatology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Yingying DaiDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Yang WangDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Hanying YiDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Shiyu WangDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Dongbo LiuDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Kun SongDepartment of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, China.
Wenwu PeiDepartment of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, China.
Ziyang HongDepartment of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, China.
Wei ZhangDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Weihua HuangDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Gan ZhouDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Shan CaoDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Howard McLeodDepartment of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China.
Cong PengDepartment of Dermatology, Xiangya Hospital Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0001-7104-5490
Ling Chen *Department of Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, Hunan, China heyijing@csu.edu.cn chen-ling@csu.edu.cn.
Yijing He *Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan, China heyijing@csu.edu.cn chen-ling@csu.edu.cn.ORCID http://orcid.org/0000-0001-5831-641X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic stress is known to promote cancer progression, in part by modulating immune responses through the β

methodsIn vivo and in vitro experiments were performed to evaluate the role of ADRB2 in melanoma models, including its effects on T cells. RNA sequencing analysis highlighted the importance of the transcription factor SRY-related HMG-box 10 (SOX10), which transcriptionally regulates programmed death-ligand 1 (PD-L1). This regulatory role was further validated using luciferase reporter assays and chromatin immunoprecipitation-PCR assays. Mechanistic studies focused on ADRB2 signaling through protein kinase A (PKA) and its downstream target SOX10. To investigate SOX10's role in mediating the effects of ADRB2, knockdown and overexpression experiments were conducted. Additionally, similar studies in colorectal cancer (CRC) models confirmed the conserved function of the ADRB2-SOX10-PD-L1 axis.

resultsThis study explores the role of ADRB2 in regulating tumor PD-L1 expression and T cell functionality, offering insights for cancer immunotherapy. Clinical data revealed that patients with melanoma with high ADRB2 expression responded better to programmed cell death protein 1 inhibitors. In melanoma models, ADRB2 inhibition reduced PD-L1 expression, enhanced T cell infiltration, and promoted antitumor immunity, while ADRB2 activation had the opposite effect. Mechanistically, ADRB2 signaling through PKA upregulated SOX10, which transcriptionally modulates PD-L1. SOX10 knockdown replicated the effects of ADRB2 inhibition, while SOX10 overexpression reversed them. Similar findings in CRC models confirmed the conserved role of the ADRB2-SOX10-PD-L1 axis. Targeting ADRB2 and SOX10 may enhance immune checkpoint inhibitor efficacy in cancer treatment.

conclusionsThese findings underscore the potential of ADRB2 and SOX10 as therapeutic targets for mitigating stress-induced immunosuppression and for augmenting the effectiveness of immunotherapies in a variety of cancer types.

Indexed as

B7-H1 AntigenReceptors, Adrenergic, beta-2SOXE Transcription FactorsT-LymphocytesTumor EscapeAnimalsCell Line, TumorFemaleHumansMiceSignal TransductionADRB2 protein, humanB7-H1 AntigenCD274 protein, humanReceptors, Adrenergic, beta-2SOX10 protein, humanSOXE Transcription Factorscolorectal cancerskin cancerstress

Identifiers

PMID40514069
PMCPMC12164648

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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.