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Sequential adjustment of cytotoxic T lymphocyte densities improves efficacy in controlling tumor growth

Kazhen, Roxana and Muller, Sabina and Lafouresse, Fanny and Valitutti, Salvatore and Cussat-Blanc, Sylvain Sequential adjustment of cytotoxic T lymphocyte densities improves efficacy in controlling tumor growth. (2019) Scientific Reports, 9 (12308). ISSN 2045-2322

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Official URL: https://doi.org/10.1038/s41598-019-48711-2

Abstract

Understanding the human cytotoxic T lymphocyte (CTL) biology is crucial to develop novel strategies aiming at maximizing their lytic capacity against cancer cells. Here we introduce an agent-based model, calibrated on population-scale experimental data that allows quantifying human CTL per capita killing. Our model highlights higher individual CTL killing capacity at lower CTL densities and fits experimental data of human melanoma cell killing. The model allows extending the analysis over prolonged time frames, difficult to investigate experimentally, and reveals that initial high CTL densities hamper efficacy to control melanoma growth. Computational analysis forecasts that sequential addition of fresh CTL cohorts improves tumor growth control. In vivo experimental data, obtained in a mouse melanoma model, confirm this prediction. Taken together, our results unveil the impact that sequential adjustment of cellular densities has on enhancing CTL efficacy over long-term confrontation with tumor cells. In perspective, they can be instrumental to refine CTL-based therapeutic strategies aiming at controlling tumor growth.

Item Type:Article
Additional Information:https://www.nature.com/articles/s41598-019-48711-2
HAL Id:hal-02940967
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Université de Toulouse > Université Toulouse - Jean Jaurès - UT2J (FRANCE)
Université de Toulouse > Université Toulouse 1 Capitole - UT1 (FRANCE)
Laboratory name:
Funders:
INSERM : Institut national de la santé et de la recherche médicale ; UMR 1043 et UMR 1037 (France) - ANR : Agence nationale de la recherche (France) - TOUCAN : Laboratoire d’Excellence Toulouse Cancer (France) - Région Occitanie (France) - Cancéropôle GSO : Cancéropôle Grand Sud-Ouest (France) - Fondation Toulouse Cancer Santé (France) - Ligue Nationale contre le Cancer - Equipe labellisée 2018 (France)
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Deposited On:02 Sep 2020 09:18

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