Evidence map›Paper›PMID 41260902›Full record

ArticleJournal for immunotherapy of cancer2025

Oligoclonal tumor-specific CD8 T-cell revival and IRE1α/XBP1-GDF15-mediated immunosuppressive niches determine neoadjuvant chemoimmunotherapy efficacy in cervical cancer.

Guangxu Cao, Yuhan Wang, Huimin Zeng, Yong Zhi, Yi Guo, Mengting Xu, Yetian Ruan, Ying Wang, Yuhang Xiao, Jianqiao Lu and 6 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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
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

16 authors.

Guangxu Cao *Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuhan Wang *Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0001-9134-0091
Huimin Zeng *Department of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yong Zhi *State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Yi GuoDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Mengting XuDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yetian RuanDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Ying WangDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuhang XiaoDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Jianqiao LuDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Ka Yu TseDepartment of Obstetrics and Gynecology, Queen Mary Hospital, Hong Kong, Hong Kong.
Jinli GaoDepartment of Pathology, Tongji University Affilliated East Hospital, Shanghai, Shanghai, China.
Qingfeng ZhangKey Laboratory of Pathogen-Host Interaction (Tongji University), Ministry of Education, School of Medicine, Tongji University, Shanghai, China.
Chenfei WangKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, Shanghai, China fang_li@tongji.edu.cn hanzq2003@126.com 08chenfeiwang@tongji.edu.cn.ORCID http://orcid.org/0000-0001-7573-3768
Zhiqiang HanDepartment of Obstetrics and Gynecology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China fang_li@tongji.edu.cn hanzq2003@126.com 08chenfeiwang@tongji.edu.cn.
Fang LiDepartment of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China fang_li@tongji.edu.cn hanzq2003@126.com 08chenfeiwang@tongji.edu.cn.ORCID http://orcid.org/0000-0003-0342-3941

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeoadjuvant chemoimmunotherapy (NACI) shows promise for locally advanced cervical cancer (LACC), but drug-tolerant persister (DTP) cells and immunosuppressive microenvironmental adaptations limit clinical efficacy. The underlying determinants governing heterogeneous responses to NACI regimens remain poorly understood, particularly regarding how dynamic tumor-immune interactions shape therapeutic outcomes.

methodsWe characterized microenvironmental dynamics in patients with LACC by integrating single-cell RNA sequencing (RNA-seq), single-cell VDJ sequencing (n=10, five paired pre-NACI/post-NACI samples) and spatial transcriptomics (ChiCTR2300072535). Pathological response was assessed using major pathological response criteria. The findings were validated in an independent NACI cohort (n=23 with RNA-seq), multiplex immunohistochemistry (mIHC) analysis of six surgically resected specimens, as well as functional in vitro and murine models.

resultsMPR patients exhibited cytotoxic revival via oligoclonal expansion of tumor-reactive CD8+T cell clones and CCR5-mediated myeloid-T cell crosstalk. Conversely, non-MPR tumors exhibited endoplasmic reticulum (ER) stress-adapted DTP cells with elevated ER stress signaling, accompanied by a deficiency in tumor-specific T-cell clone expansion and an accumulation of transforming growth factor beta receptor 2 (TGFBR2) + myeloid DTP niches. Mechanistically, ER stress signaling via the inositol‑requiring enzyme 1 alpha (IRE1α) / X‑box binding protein 1 (XBP1) axis induces growth differentiation factor 15 (GDF15) production in DTP cells, contributing to treatment‑resistant microdomains. Pharmacological IRE1α inhibition synergized with chemoimmunotherapy to eradicate DTP populations in murine models.

conclusionsThis study provides critical insights that NACI resistance stems from adaptive ER stress signaling in DTP cells and spatially organized immunosuppressive networks. Targeting the IRE1α/XBP1-GDF15 axis represents an actionable strategy to reprogram microenvironmental ecology and improve immunotherapy outcomes.

Indexed as

CD8-Positive T-LymphocytesEndoribonucleasesImmunotherapyNeoadjuvant TherapyProtein Serine-Threonine KinasesUterine Cervical NeoplasmsX-Box Binding Protein 1AnimalsFemaleHumansMiceTumor MicroenvironmentEndoribonucleasesERN1 protein, humanProtein Serine-Threonine KinasesX-Box Binding Protein 1XBP1 protein, humanCervical CancerImmune Checkpoint InhibitorMajor pathologic response - MPRTumor infiltrating lymphocyte - TILTumor Microenvironment

Identifiers

PMID41260902
PMCPMC12636911

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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.