Evidence map›Paper›PMID 41142474›Full record

ArticleTherapeutic advances in medical oncology2025

Virtual multiplex immunofluorescence identifies lymphocyte subsets predictive of response to neoadjuvant therapy.

Anran Li, Madeleine Torcasso, Anna Woodard, Hanna Hieromnimon, Jonathan Trujillo, Long Nguyen, Margarite Matossian, James Dolezal, Rebecca Abraham, Marcus R Clark and 5 more

Abstract read
In one paragraph

Article in Therapeutic advances in medical oncology, 2025. 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

15 authors.

Anran LiDepartment of Medicine, University of Chicago, Chicago, IL, USA.ORCID https://orcid.org/0009-0002-5226-2398
Madeleine TorcassoDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Anna WoodardDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Hanna HieromnimonDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Jonathan TrujilloDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Long NguyenDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Margarite MatossianDepartment of Medicine, University of Chicago, Chicago, IL, USA.
James DolezalGeisinger Cancer Institute, Danville, PA, USA.
Rebecca AbrahamDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Marcus R ClarkDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Galina KhramtsovaDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Yuanyuan ZhaDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Maryellen L GigerDepartment of Radiology, University of Chicago, Chicago, IL, USA.
Alexander T PearsonDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Frederick M HowardSection of Hematology Oncology, Department of Medicine, The University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637, USA.ORCID https://orcid.org/0000-0002-6039-1141

Funding

BASIC RESEARCH TRAINING IN MEDICAL ONCOLOGYT32CA009566 · NCI · UNIVERSITY OF CHICAGO · PI OLUFUNMILAYO F. OLOPADE · 1987 to 2026
$10.5M
NCI NIH HHS T32 CA009566
6 · The paper itself

Abstract

Background: Hematoxylin and eosin (H&E) staining is routine in pathology but lacks cellular specificity. Multiplex immunofluorescence (mIF) captures spatial immune relationships in tumors, but cost and complexity limit clinical application. Novel approaches to yield similar information from readily available tumor histology are needed. Objectives: Develop and validate a novel deep learning tool capable of translating standard H&E-stained histopathology images into high-fidelity synthetic mIF images that preserve immune cell information predictive of treatment response in breast cancer. Design: Comparative model evaluation and predictive modeling in a retrospective breast cancer cohort. Methods: Core-needle biopsies from 17 triple-negative breast cancer cases underwent mIF imaging. Hematoxylin and eosin and mIF images for DAPI (nuclei), pan-CK (tumor), CD3/CD4/CD8 (T-cells), and CD20 (B cells) were aligned. A pipeline outperforming standard Pix2Pix and CycleGAN image translation networks was developed, "multiplex Synthetic Immunofluoresence Generated through H&E Translation" (mSIGHT), which integrates a registration network to overcome misalignment between the input and target images. Generated images were evaluated with pixel-level metrics and biological metrics, including cell density and cell-to-cell adjacency. The pipeline was then applied to an external cohort to assess associations between predicted immune features and pathologic response to neoadjuvant chemotherapy. Results: Generated images preserved immune cell distributions and proximity metrics correlated to the ground truth cell counts. In a cohort of 218 breast cancer cases treated with neoadjuvant chemotherapy, predicted density of CD8+ T cells was significantly associated with complete response (adjusted odds ratio 1.89, 95% confidence interval 1.23-2.80, Conclusion: The mSIGHT pipeline enables translation of routine H&E slides into virtual mIF images with interpretable immune biomarkers, offering a scalable and affordable alternative to multiplex imaging. It also identifies immune features predictive of therapeutic response and has the potential to assist in the personalization of neoadjuvant therapy.

Indexed as

deep learningimage translationmultiplex immunofluorescenceneoadjuvant therapytriple-negative breast cancertumor microenvironment

Identifiers

PMID41142474
PMCPMC12547128

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.