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Peer-Reviewed Publication
Nat Commun2026;17(1):837.February 3, 2026Journal Article

Metabolic characterization of tumor-immune interactions by multiplexed immunofluorescence reveals spatial mechanisms of immunotherapy response in non-small cell lung carcinoma (NSCLC).

James Monkman1,2, Aaron Kilgallon1,2, Clara Lawler1, Rafael Tubelleza1,2, Thazin Nwe Aung3, Jonathan H Warrell3, Ioannis Vathiotis3, Ioannis P Trontzas3, Niki Gavrielatou3, Nay Nwe Nyein Chan3, Rotem Czertok4, Shai Bookstein4, Ken O'Byrne5, Ettai Markovits4, David L Rimm3, Arutha Kulasinghe6,7
1Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.
2Queensland Spatial Biology Centre, Wesley Research Institute, Auchenflower, QLD, Australia.
3Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
4Nucleai, Tel-Aviv, Israel.
5Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
6Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia. Arutha.kulasinghe@uq.edu.au.
7Queensland Spatial Biology Centre, Wesley Research Institute, Auchenflower, QLD, Australia. Arutha.kulasinghe@uq.edu.au.

Abstract

Immune checkpoint inhibitors (ICI) have improved clinical outcomes for some patients with advanced NSCLC, however a substantial proportion of patients remain treatment resistant. Here we analyze the NSCLC tumor microenvironment (TME) using multiplexed immunofluorescence (mIF) of biopsies taken from patients prior to ICI treatment. We apply a deep-learning model to classify the cellular phenotypes…

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