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September 24, 2025Advanced Therapeutics1 citationsOpen Access

A Systematic Approach to Analyze T Cell Migration: Application to Mouse Melanoma Tumors

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NMNikolaos MemmosJMJason S. MitchellBFBrian T. Fife

Key Points

  • CD8+ T cells display a two-state migration dynamic, suggesting distinct behavior in tumor environments.
  • The proposed algorithm uses Hidden Markov Model to capture varying migration states in T cells effectively.
  • Migration analysis provides insights into T cell speeds, distinguishing true variability from random fluctuations.
  • Two-photon microscopy enabled tracking of different avidity T cells in melanoma tumors for comprehensive analysis.

Abstract

Abstract T cells must assess and choose between surveilling large areas, but also engage efficiently with the target cells. This process is translated into variations in the speed and turning angle of T cells. In this study, a generalized algorithm is proposed to analyze cell migration data with focus on CD8+ T cells, using clustering technique to identify the number of different migration states and Hidden Markov Model (HMM)to capture the dynamical switching between them. The algorithm only requires a set of position observations in a series of times, independent of other factors. While this study focuses on CD8+ T cell migration, this approach can potentially be used broadly to study the migration of other cell types as well. For the current analysis, low and high avidity T cells in melanoma tumors are tracked ex vivo using two‐photon microscopy. These findings suggest that CD8+ T cells follow a two‐state migration dynamic, with one state being faster, while the other slower and more localized. Moreover, a statistical methodology is established to analyze T cell migration to assess whether there is true variability in cell speeds as distinguished from stochastic fluctuations about a single speed, and it can be applied across different experimental platforms.

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Cite This Study

Memmos et al. (2025) studied this question.

synapsesocial.com/papers/68d6d8978b2b6861e4c3ecc8https://doi.org/10.1002/adtp.202500169
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