BLINK: Behavioral Latent Modeling of NK Cell Cytotoxicity

๐Ÿ“… 2026-03-05
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๐Ÿค– AI Summary
Natural killer (NK) cell cytotoxicity is difficult to assess accurately from single-frame images, necessitating modeling of their dynamic, long-term interactions with tumor cells. To address this, this work proposes BLINKโ€”a trajectory-based recurrent state-space model that learns latent dynamics from partially observed NKโ€“tumor interaction sequences to predict time-accumulated apoptosis increments and thereby infer final killing outcomes. This study introduces, for the first time, trajectory-level latent behavior modeling into NK cell cytotoxicity research, enabling interpretable segmentation of interaction phases, organization of behavioral patterns, and prediction of future killing efficacy. Evaluated on long-term time-lapse imaging data, BLINK significantly improves killing detection accuracy and yields structured, interpretable representations of NK cell behavior.

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๐Ÿ“ Abstract
Machine learning models of cellular interaction dynamics hold promise for understanding cell behavior. Natural killer (NK) cell cytotoxicity is a prominent example of such interaction dynamics and is commonly studied using time-resolved multi-channel fluorescence microscopy. Although tumor cell death events can be annotated at single frames, NK cytotoxic outcome emerges over time from cellular interactions and cannot be reliably inferred from frame-wise classification alone. We introduce BLINK, a trajectory-based recurrent state-space model that serves as a cell world model for NK-tumor interactions. BLINK learns latent interaction dynamics from partially observed NK-tumor interaction sequences and predicts apoptosis increments that accumulate into cytotoxic outcomes. Experiments on long-term time-lapse NK-tumor recordings show improved cytotoxic outcome detection and enable forecasting of future outcomes, together with an interpretable latent representation that organizes NK trajectories into coherent behavioral modes and temporally structured interaction phases. BLINK provides a unified framework for quantitative evaluation and structured modeling of NK cytotoxic behavior at the single-cell level.
Problem

Research questions and friction points this paper is trying to address.

NK cell cytotoxicity
cellular interaction dynamics
time-resolved microscopy
apoptosis prediction
single-cell behavior
Innovation

Methods, ideas, or system contributions that make the work stand out.

trajectory-based modeling
recurrent state-space model
latent interaction dynamics
NK cell cytotoxicity
interpretable representation
Iman Nematollahi
Iman Nematollahi
Researcher, University of Freiburg
World ModelsReinforcement LearningRobot Learning
J
Jose Francisco Villena-Ossa
Institute for Transfusion Medicine and Gene Therapy, University Medical Center Freiburg, Freiburg, Germany
A
Alina Moter
Goethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany
K
Kiana Farhadyar
Department of Computer Science, University of Freiburg, Freiburg, Germany
Gabriel Kalweit
Gabriel Kalweit
University of Freiburg
Reinforcement LearningMachine LearningDeep Learning
Abhinav Valada
Abhinav Valada
Professor & Director of Robot Learning Lab, University of Freiburg
RoboticsMachine LearningComputer VisionArtificial Intelligence
T
Toni Cathomen
Institute for Transfusion Medicine and Gene Therapy, University Medical Center Freiburg, Freiburg, Germany
E
Evelyn Ullrich
Goethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany
M
Maria Kalweit
Collaborative Research Institute Intelligent Oncology (CRIION), Freiburg, Germany; Department of Computer Science, University of Freiburg, Freiburg, Germany; IMBIT//BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany