Evidence map›Paper›PMID 41916292›Full record

ArticleCell reports. Medicine2026

A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.

Shiyou Wei, Yulan Deng, Jinho Lee, Hongbin Lan, Zhenyu Yang, Marilyne Labrie, Courtney B Betts, Hao Duan, Benjamin Tate, Joanna Pucilowska and 45 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. 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. 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

55 authors.

Shiyou WeiDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Yulan DengDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Jinho LeeKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA.
Hongbin LanFaculty of Dentistry, the University of Hong Kong, Sai Ying Pun, Hong Kong 999077, China.
Zhenyu YangDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Marilyne LabrieDepartment of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC 819821, Canada.
Courtney B BettsKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Knight Cancer Institute, Department of Cell, Developmental & Cancer Biology, Oregon Health and Sciences University, Portland, OR 97239, USA.
Hao DuanDepartment of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Benjamin TateKnight Cancer Institute, Department of Cell, Developmental & Cancer Biology, Oregon Health and Sciences University, Portland, OR 97239, USA; Immune Monitoring and Cancer Omics Services, Oregon Health and Science University, Portland, OR 97239, USA.
Joanna PucilowskaKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Immune Monitoring and Cancer Omics Services, Oregon Health and Science University, Portland, OR 97239, USA.
Dennie FrederickBroad Institute, Boston, MA 02142, USA.
Aleigha R LawlessDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Tatyana SharovaDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Yuanzhong YangDepartment of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Wanming HuDepartment of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Georgia M BeasleyDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Lynn M SchuchterAbramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Xiuqi WangFaculty of Dentistry, the University of Hong Kong, Sai Ying Pun, Hong Kong 999077, China.
Wei XuDepartment of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gen YongKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Cancer Early Detection Advanced Research Center, Oregon Health and Science University, Portland, OR 97239, USA.
Megan E G VandenbergKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA.
Drew A TorigianDepartment of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Shamilene SivagnanamKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Knight Cancer Institute, Department of Cell, Developmental & Cancer Biology, Oregon Health and Sciences University, Portland, OR 97239, USA.
Kuang DuDepartment of Computer Science, Ying Wu College of Computing, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Eric SugarmanPhiladelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA.
Suzanne McGettiganAbramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cathy ZhengAbramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Rami N Al-RohilDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Maria A SelimDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Michael B DattoDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Giselle Y LópezDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USA; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Smita K NairDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
David M AshleyThe Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.
Xiaowei XuAbramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Ravi K AmaravadiBroad Institute, Boston, MA 02142, USA; Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Giorgos C KarakousisDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Donald M O'RourkeDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Steven BremDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Bert W O'MalleyDepartment of Otorhinolaryngology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Gokhan DemirkanNanoString Technologies, Inc., Seattle, WA 98109, USA.
Shuangxing YuDepartment of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Yiling LuDepartment of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Todd CampKnight Diagnostics Laboratory, Oregon Health and Science University, Portland, OR 97239, USA.
Janice A PattersonKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Knight Diagnostics Laboratory, Oregon Health and Science University, Portland, OR 97239, USA.
Zhi WeiDepartment of Computer Science, Ying Wu College of Computing, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Christopher CorlessKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Knight Diagnostics Laboratory, Oregon Health and Science University, Portland, OR 97239, USA.
Dmitry I GabrilovichR&D Oncology, AstraZeneca, Gaithersburg, MD 20878, USA.
Yonggao MouDepartment of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Keith T FlahertyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Lisa M CoussensKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA; Knight Cancer Institute, Department of Cell, Developmental & Cancer Biology, Oregon Health and Sciences University, Portland, OR 97239, USA. Electronic address: coussenl@ohsu.edu.
Genevieve BolandDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: gmboland@mgh.harvard.edu.
Meenhard HerlynMolecular & Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA; The Wistar Institute Melanoma Research Center, The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: herlynm@wistar.org.
Gordon MillsKnight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97239, USA. Electronic address: millsg@ohsu.edu.
Lunxu LiuDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: lunxu_liu@aliyun.com.
Gao ZhangFaculty of Dentistry, the University of Hong Kong, Sai Ying Pun, Hong Kong 999077, China. Electronic address: gzhang6@me.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite advances in immune checkpoint blockade, resistance in metastatic melanoma remains a major challenge. To decode resistance mechanisms, we generate a comprehensive longitudinal, multi-omic, and spatial atlas of 45 tumor samples across 10 patients. Analysis reveals resistant tumors undergo convergent evolution toward a shared, spatially organized immunosuppressive ecosystem. We identify a structural mechanism characterized by spatial partitioning of immune checkpoints, where B7-H3 dominates MITF-high niches while IDO1 characterizes MITF-low zones. Furthermore, integrated single-cell and spatial analysis identifies a specific malignant subclone (c1) and a distinct architectural niche (RCN3), both exhibiting aberrant PI3K-mTOR signaling. Notably, c1 promotes the "ignored tumor" phenotype via FN1-ITGB1 and GDF15 signaling. Validated across independent cohorts, these spatial and molecular signatures predict poor survival and point to actionable targets. Ultimately, our study elucidates the spatial logic of resistance and provides a rationale for translating multi-omic discoveries into actionable, personalized therapeutic strategies.

Indexed as

Drug Resistance, NeoplasmMelanomaTumor MicroenvironmentHumansLongitudinal StudiesMultiomicsSignal TransductionTOR Serine-Threonine KinasesTOR Serine-Threonine Kinasesdynamic evolutionimmune checkpoint blockademelanomaresistance

Identifiers

PMID41916292
PMCPMC13130630

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.