ICOS-ImmunoPET Monitors T Cell Activation After Combination Immune Checkpoint Blockade in a Mouse Model of Melanoma Brain Metastasis.

Overview

1. Department of Electrical Engineering, Stanford University, Stanford, California, USA
2. Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, California, USA
3. Department of Neurosurgery, Stanford University, Stanford, California, USA
4. Lunaphore Technologies, Tolochenaz, Switzerland
5. Department of Pathology, Stanford University, Stanford, California, USA
6. Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA

Abstract

Immune checkpoint inhibitors (ICIs) have transformed outcomes for melanoma brain metastases (MBM), yet early response assessment remains challenging because currently available tools such as magnetic resonance imaging (MRI) lack molecular specificity and are confounded by pseudoprogression. Antibody‐based positron emission tomography (immunoPET) is a highly sensitive and specific molecular imaging technique that enables noninvasive, whole‐body visualization of immune dynamics in vivo. The inducible T cell costimulatory receptor (ICOS) is a promising biomarker of therapy‐induced T cell activation. Here, a previously validated tracer, [89Zr]DFO‐ICOS mAb, is used to track activated T cells in a murine MBM model treated with combined anti‐PD‐1/anti‐CTLA‐4 therapy, and immunoPET signal is shown to correspond with therapeutic response and intratumoral T cell activation. To establish clinical relevance of ICOS‐immunoPET, single‐cell RNA sequencing data from 6 human MBM specimens are reanalyzed, revealing significantly higher ICOS expression accompanied by coordinated activation signatures in ICI‐treated tumors. These findings support ICOS‐immunoPET as a promising strategy for earlier, noninvasive, functionally informative assessment of immunotherapy response, with potential to improve patient stratification in brain metastases.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE193745 — at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

All data associated with this study are present in the paper and/or the Supplementary Information. The raw data files for the previously published and publicly available scRNA‐seq data are available in the Gene Expression Omnibus database (GSE193745 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193745)).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, pages, dates, 11 authors, 5 keywords, 5 funders, 44 references.

Cite

This paper

Kuo, R. C., Verma, R., Nagy, S. C., Kalita, M., Aubert, S., Ballesteros‐Álvarez, J., Almeida, P. M., Vogel, H., Alam, I. S., Lim, M., & James, M. L. (2026). ICOS-ImmunoPET Monitors T Cell Activation After Combination Immune Checkpoint Blockade in a Mouse Model of Melanoma Brain Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e76803. https://doi.org/10.1002/advs.76803

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