Evidence map›Paper›PMID 42236958›Full record

ArticleNature biotechnology2026

Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors.

Guolan Lu, John W Hickey, Maximilian Haist, Xulei Qin, Emily Zhao, Abdullah Naveed, Erna Forgo, Marc-A Baertsch, Lucas Mani, Xavier Rovira-Clavé and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

26 authors.

Guolan LuDepartment of Urology, Stanford University School of Medicine, Stanford, CA, USA. guolanlu@stanford.edu.ORCID http://orcid.org/0000-0002-5023-3465
John W HickeyDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Maximilian HaistDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6720-7570
Xulei QinDepartment of Surgery, Stanford University, Stanford, CA, USA.
Emily ZhaoDepartment of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Abdullah NaveedDepartment of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA.
Erna ForgoDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Marc-A BaertschDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Lucas ManiDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Xavier Rovira-ClavéDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Andrey FinegershDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Yury GoltsevDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4079-7969
Chiara CaraccioDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3580-1348
Nynke S van den BergDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Marisa HomDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Deana R ColburgDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Brock A MartinDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Christina S KongDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2098-6842
Natalie S LuiDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6602-6372
George A FisherDepartment of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
A Dimitrios ColevasDepartment of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
Robert B WestDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Greg M ThurberDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-7570-2080
George A PoultsidesDepartment of Surgery, Stanford University, Stanford, CA, USA.
Garry P NolanDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. gnolan@stanford.edu.ORCID http://orcid.org/0000-0002-8862-9043
Eben L RosenthalDepartment of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA. e.rosenthal@vumc.org.ORCID http://orcid.org/0000-0003-0294-5203

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Pauline Funchain · 2007 to 2026
$71.4M
Stanford Molecular Imaging Scholars (SMIS) ProgramT32CA118681 · NCI · STANFORD UNIVERSITY · PI CRAIG S LEVIN · 2016 to 2026
$4.3M
Prototype optical device for image guided surgery with panitumumab-IRDye800R01CA190306 · NCI · STANFORD UNIVERSITY · PI ROSENTHAL, EBEN L. · 2015 to 2019
$2.6M
Highly Sensitive Detection of Occult Pancreatic Cancer Using Intraoperative Molecular ImagingR01CA273035 · NCI · STANFORD UNIVERSITY · PI George Poultsides · 2023 to 2026
$1.9M
Integrating Spatial Omics and Drug Imaging to Dissect the Role of Pancreatic Tumor Microenvironment in Drug ResistanceR00CA267171 · NCI · STANFORD UNIVERSITY · PI Guolan Lu · 2024 to 2026
$747k
Integrating Spatial Omics and Drug Imaging to Dissect the Role of Pancreatic Tumor Microenvironment in Drug ResistanceK99CA267171 · NCI · STANFORD UNIVERSITY · PI LU, GUOLAN · 2022 to 2023
$295k
American Cancer Society (American Cancer Society, Inc.) MBGII-24-1255495-01-MBGDeutsche Forschungsgemeinschaft (German Research Foundation) HA 9793/1-1International Myeloma Foundation (IMF) Career Development AwardNCI NIH HHS K99 CA267171NCI NIH HHS P30 CA124435NCI NIH HHS R00 CA267171NCI NIH HHS R01 CA190306NCI NIH HHS R01 CA273035NCI NIH HHS T32 CA118681U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) NIH R01CA190306U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) NIH R01CA273035U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA124435U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R00CA267171U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32CA118681
6 · The paper itself

Abstract

The development of effective antibody therapeutics has been hampered by a lack of methods to measure drug delivery and activity within tumors at single-cell resolution. Here we introduce single-cell spatial pharmacobiology (SSP), an experimental and analytical framework that integrates in situ imaging of a systemically infused, fluorescently labeled therapeutic antibody with high-plex spatial proteomics to quantify antibody distribution, target engagement and tumor microenvironment (TME) architecture. We applied SSP to tumor tissues from participants with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma who received the antibody panitumumab-IRDye800 in phase 1 trials. SSP identified pronounced spatial heterogeneity in single-cell drug delivery and target engagement, shaped by conserved stromal barriers, including periostin-rich extracellular matrix assemblies and fibroblast-activation-protein-positive cancer-associated fibroblast neighborhoods, which were associated with reduced antibody delivery in both tumor types. SSP measures drug-target-TME interactions in human tumors and can support studies of resistance mechanisms, dosing strategies and discovery of spatial biomarkers for precision oncology.

Identifiers

PMID42236958
PMCPMC13390730

What Socratic 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 Socratic graph.