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

Abstract : 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.
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Submitted on : Monday, September 12, 2022 - 2:25:32 PM
Last modification on : Thursday, September 15, 2022 - 4:11:24 AM


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Gustave Ronteix, Shreyansh Jain, Christelle Angely, Marine Cazaux, Roxana Khazen, et al.. High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing. Nature Communications, Nature Publishing Group, 2022, 13 (1), pp.3111. ⟨10.1038/s41467-022-30575-2⟩. ⟨pasteur-03775301⟩



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