Evidence map›Paper›PMID 41486103›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Stress-Programmed Immune Niches Fuel TNFR2+ Treg Activation and Drive Neoadjuvant Chemotherapy Resistance in Breast Cancer.

Zhibo Shao, Xuliren Wang, Han Zhu, Ling Yao, Qi Zhang, Zihan Zhai, Xinyi Lv, Xinyuan Xia, Yi Zhang, Xinya Lu and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

19 authors.

Zhibo ShaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xuliren WangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Han ZhuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Ling YaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Qi ZhangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Zihan ZhaiDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinyi LvDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinyuan XiaDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Yi ZhangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinya LuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinyi QuanDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Jiawen YangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinwei LiDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Jieyi DongDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Zhi-Ming ShaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Ruoxi WangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Bingqiu XiuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Jiong WuDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Sheng ChenDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.ORCID https://orcid.org/0000-0003-3530-1287

Funding

National Natural Science Foundation of China 82203097
6 · The paper itself

Abstract

The tumor microenvironment (TME) harbors diverse immune cell states that shape therapeutic outcomes in breast cancer. Here, we identify a conserved stress-programmed cellular module as a key responder to neoadjuvant therapies in breast cancer, characterized by coordinated heat shock gene expression across multiple immune cells, based on single-cell transcriptomic data from neoadjuvant chemotherapy-treated patients. We discover that this multicellular program enhances the effector fate of regulatory T cells (Tregs) via chronic and TME-wide TNFα signaling, compromising the efficacy of neoadjuvant chemotherapy. TNFα signaling, typically considered an antitumor cytokine, is paradoxically elevated in nonresponders both pre- and post-treatment, with a particularly prominent TNFα-TNFR2 interaction. Blocking this axis, with or without chemotherapy, significantly suppresses tumor growth without observable toxicities. Our findings highlight the immune-editing role of stress-programmed Effector regulatory T cells, Neoadjuvant chemotherapy, Stress-programmed immune states, TNF α -TNFR2 axis, breast cancercell states and support their therapeutic potential as a rational target in breast cancer.

Indexed as

Breast NeoplasmsDrug Resistance, NeoplasmNeoadjuvant TherapyReceptors, Tumor Necrosis Factor, Type IIT-Lymphocytes, RegulatoryTumor MicroenvironmentAnimalsFemaleHumansMiceTumor Necrosis Factor-alphaReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphabreast cancereffector regulatory T cellsneoadjuvant chemotherapystress‐programmed immune statesTNFα‐TNFR2 axis

Identifiers

PMID41486103
PMCPMC12970206

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.