High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing

Autor: Gustave Ronteix, Shreyansh Jain, Christelle Angely, Marine Cazaux, Roxana Khazen, Philippe Bousso, Charles N. Baroud
Přispěvatelé: Microfluidique Physique et Bio-ingénierie - Physical Microfluidics and Bioengineering, Institut Pasteur [Paris] (IP)-École polytechnique (X)-Université Paris Cité (UPCité)-Institut Polytechnique de Paris (IP Paris), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), P.B. is funded by Institut Pasteur, Inserm and an advanced grant from the European Research Council (ENLIGHTEN). G.R. is funded by the Direction Générale de l’Armement. The authors acknowledge the support of the Biomaterials and Microfluidics platform and the FabLab at Institut Pasteur., The authors acknowledge enlightening discussions with Clément Roussel, Andrey Aristov, Raphael Tomasi, Gabriel Amselem and all members of the Baroud team. Raphael Voituriez is gratefully acknowledged for his comments on the probabilistic descriptions., European Project: 741167,ERC-2016-ADG,ENLIGHTEN(2018), HUGOT, Bérengère, INTEGRATION AND PROPAGATION OF IMMUNOLOGICAL SIGNALS DURING CANCER AND INFECTION - ENLIGHTEN - 2018-01-01 - 2022-12-31 - 741167 - VALID
Rok vydání: 2021
Předmět:
Zdroj: Nature Communications
Nature Communications, 2022, 13 (1), pp.3111. ⟨10.1038/s41467-022-30575-2⟩
ISSN: 2041-1723
DOI: 10.1038/s41467-022-30575-2⟩
Popis: Cytotoxic T cells are important components of natural anti-tumor immunity and are harnessed in tumor immunotherapies. Immune responses to tumors and immune therapy outcomes largely vary among individuals, but very few studies examine the contribution of intrinsic behavior of the T cells to this heterogeneity. Here we show the development of a microfluidic-based in vitro method to track the outcome of antigen-specific T cell activity on many individual cancer spheroids simultaneously at high spatiotemporal resolution, which we call Multiscale Immuno-Oncology on-Chip System (MIOCS). By combining parallel measurements of T cell behaviors and tumor fates with probabilistic modeling, we establish that the first recruited T cells initiate a positive feedback loop to accelerate further recruitment to the spheroid. We also provide evidence that cooperation between T cells on the spheroid during the killing phase facilitates tumor destruction. Thus, we propose that both T cell accumulation and killing function rely on collective behaviors rather than simply reflecting the sum of individual T cell activities, and the possibility to track many replicates of immune cell-tumor interactions with the level of detail our system provides may contribute to our understanding of immune response heterogeneity.
Databáze: OpenAIRE
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