Evidence map›Paper›PMID 42865119›Full record

ArticleeLife2026

JAK-STAT pathway heterogeneity governs immunotherapy response in breast cancer.

Jianbo Zhou, Heng Zhang, Hailin Tang, Lei Yu, Fu Peng

Abstract read
In one paragraph

Article in eLife, 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
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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

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

5 authors.

Jianbo Zhou *West China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.ORCID https://orcid.org/0000-0001-5781-5145
Heng Zhang *West China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Hailin TangState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Lei YuChongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
Fu PengWest China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.ORCID https://orcid.org/0000-0003-0289-4426

Funding

National Natural Science Foundation of China 82003879Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources SKLTCM202205Project of Sichuan Provincial Administration of Traditional Chinese Medicine 2022C001Project of Sichuan Provincial Administration of Traditional Chinese Medicine 2024ZD02Project of State Administration of Traditional Chinese Medicine of China ZYYCXTD-D-202209Science and Technology Department of Sichuan Province 2023NSFSC1928Science and Technology Department of Sichuan Province 2023NSFSC1992
6 · The paper itself

Abstract

The JAK-STAT pathway (JSP) is a well-known oncogenic cascade; however, recent clinical trials have detected JSP upregulation in breast cancer following anti-PD-1 immunotherapy. This paradoxical observation warrants further investigation into JSP's intercellular heterogeneity, tumor dynamics, molecular mechanisms, and clinical implications for immunotherapy. JSP expression showed dynamic shifts during breast cancer progression, with higher levels in T cells and paracancerous epithelial cells. In human breast cancer tumor cells, elevated JSP is highly correlated with malignant phenotypes. JSP-high tumor cells overexpressed oncogenic pathways, while exhibiting increased immunosuppressive signaling via the MIF-CD74 signaling axis. In T cells, higher JSP levels were associated with enhanced cytotoxic activity, improved differentiation, and reduced exhaustion, reflecting robust anti-tumor immunity. Analysis of immunotherapy datasets revealed that higher JSP levels were associated with improved responses toward PD-1 inhibitors, particularly in triple-negative breast cancer (TNBC) patients, with JSP serving as a predictive biomarker for immunotherapy sensitivity. As a key JSP component, STAT4 exerts dual roles in breast cancer: it drives tumorigenesis in malignant cells, sustains breast epithelial cell proliferation, and bolsters T-cell anti-tumor functionality, while also acting as a highly accurate biomarker for predicting immunotherapy response. This indicates that JSP targeting demands a nuanced approach: broad inhibition may impair anti-tumor immunity, and optimized therapeutic strategies paired with precise biomarkers are critical to maximize JSP's utility in breast cancer immunotherapy. Our findings highlight JSP's functional heterogeneity in epithelial, tumor, and T cells, with high JSP activity correlating with enhanced immunotherapy efficacy in breast cancer.

Indexed as

Breast NeoplasmsImmunotherapyJanus KinasesSignal TransductionSTAT Transcription FactorsCell Line, TumorFemaleHumansT-LymphocytesJanus KinasesSTAT Transcription Factorsbreast cancercancer biologyhumanimmunotherapyJAK-STAT pathway

Identifiers

PMID42865119
PMCPMC13661048

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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.