Evidence map›Paper›PMID 40832222›Full record

ArticlebioRxiv : the preprint server for biology2025

Novel Predictive Spatial Biomarker in Non-Small Cell Lung Carcinoma: The Diversity of Niches Unlocking Treatment Sensitivity (DONUTS).

Tricia R Cottrell, Jeffrey S Roskes, Michael Fotheringham, Emily Cohen, Boyang Zhang, Logan L Engle, Daphne Wang, Elizabeth Will, Joel C Sunshine, Daniel Jimenez-Sanchez and 32 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

42 authors.

Tricia R CottrellDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Jeffrey S RoskesDepartment of Physics & Astronomy, Johns Hopkins University, Baltimore, MD, USA.
Michael FotheringhamDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Emily CohenDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Boyang ZhangDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Logan L EngleDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Daphne WangDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Elizabeth WillDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Joel C SunshineDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Daniel Jimenez-SanchezDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Zhen ZengDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Justina X CaushiDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Jiajia ZhangDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Nina M D'AmianoDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Julie S DeutschDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Sonali UttamDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Katie PirieDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Darah VlaminckDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Michelle MatajDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Eman RadwanDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Alexa FioranteDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Nicole EspinosaDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Teodora PopaDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Aleksandra OgurtsovaDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Sigfredo Soto-DiazDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Margaret EminizerDepartment of Physics & Astronomy, Johns Hopkins University, Baltimore, MD, USA.
Samuel TabriskyDepartment of Physics & Astronomy, Johns Hopkins University, Baltimore, MD, USA.
Andrew JorqueraDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Jonathan SkidmoreDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Dmitry MedvedevDepartment of Physics & Astronomy, Johns Hopkins University, Baltimore, MD, USA.
Jamie E ChaftDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Julie R BrahmerDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Michael ConroyDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Joshua E ReussDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Ludmila DanilovaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Hongkai JiDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Patrick M FordeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Drew M PardollDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Kellie N SmithDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Benjamin F GreenDepartment of Dermatology, Johns Hopkins University, Baltimore, MD, USA.
Alexander S SzalayDepartment of Physics & Astronomy, Johns Hopkins University, Baltimore, MD, USA.
Janis M TaubeDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
PD-1/PD-L1 modulation in cancer therapyR01CA142779 · NCI · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M., TAUBE, JANIS M · 2010 to 2025
$8.2M
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
Immunogenomic determinants of response and resistance to neoadjuvant anti-PD-1 in resectable NSCLCR37CA251447 · NCI · JOHNS HOPKINS UNIVERSITY · PI Kellie Nicole Smith · 2021 to 2026
$2.2M
Analytical Infrastructure for Multiple Sample Single Cell Genomic DataR01HG013409 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI Hongkai Ji · 2024 to 2026
$1.1M
Comprehensive Analysis and Multi-Omics Data Integration for Cancer-Related StudiesR50CA243627 · NCI · JOHNS HOPKINS UNIVERSITY · PI Ludmila Danilova · 2019 to 2026
$975k
NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA142779NCI NIH HHS R37 CA251447NCI NIH HHS R50 CA243627NCI NIH HHS T32 CA193145NHGRI NIH HHS R01 HG013409
6 · The paper itself

Abstract

Probabilistic spatial modelling techniques developed on large-scale tumor-immune Atlases (~35M individually mapped cells; 50,000 high power fields) were used to characterize predictive features of treatment-responsive lung cancer. We identified CD8+FoxP3+ cell density as a robust pre-treatment biomarker for outcomes across disease stages and therapy types. In parallel, single-cell RNAseq studies of CD8+FoxP3+ T-cells revealed an activated, early effector phenotype, substantiating an anti-tumor role, and contrasting with CD4+FoxP3+ T-regulatory cells. A spatial biomarker was developed using an empirical probabilistic model to define the immediate cell neighbors or niche surrounding CD8+FoxP3+ cells and proximity to the tumor-stromal boundary. The resultant 'Diversity of Niches Unlocking Treatment Sensitivity (DONUTS)' are more prevalent than the CD8+FoxP3+ cells themselves, mitigating sampling error in small biopsies. Further, the DONUTS only require four markers, are additive to PD-L1, and associate with tertiary lymphoid structure counts. Taken together, the DONUTS represent a next-generation predictive biomarker poised for clinical implementation.

Indexed as

AstroPathbiomarkerCD8+FoxP3+immunotherapylung cancerneighborhoodNSCLCpathologyPD-1spatial

Identifiers

PMID40832222
PMCPMC12363902

What OpenQuestion holds

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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.