Cargando…
High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing
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 hete...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166723/ https://www.ncbi.nlm.nih.gov/pubmed/35661707 http://dx.doi.org/10.1038/s41467-022-30575-2 |
_version_ | 1784720668460318720 |
---|---|
author | Ronteix, Gustave Jain, Shreyansh Angely, Christelle Cazaux, Marine Khazen, Roxana Bousso, Philippe Baroud, Charles N. |
author_facet | Ronteix, Gustave Jain, Shreyansh Angely, Christelle Cazaux, Marine Khazen, Roxana Bousso, Philippe Baroud, Charles N. |
author_sort | Ronteix, Gustave |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9166723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91667232022-06-05 High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing Ronteix, Gustave Jain, Shreyansh Angely, Christelle Cazaux, Marine Khazen, Roxana Bousso, Philippe Baroud, Charles N. Nat Commun Article 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. Nature Publishing Group UK 2022-06-03 /pmc/articles/PMC9166723/ /pubmed/35661707 http://dx.doi.org/10.1038/s41467-022-30575-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ronteix, Gustave Jain, Shreyansh Angely, Christelle Cazaux, Marine Khazen, Roxana Bousso, Philippe Baroud, Charles N. High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title | High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title_full | High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title_fullStr | High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title_full_unstemmed | High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title_short | High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing |
title_sort | high resolution microfluidic assay and probabilistic modeling reveal cooperation between t cells in tumor killing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166723/ https://www.ncbi.nlm.nih.gov/pubmed/35661707 http://dx.doi.org/10.1038/s41467-022-30575-2 |
work_keys_str_mv | AT ronteixgustave highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT jainshreyansh highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT angelychristelle highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT cazauxmarine highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT khazenroxana highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT boussophilippe highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling AT baroudcharlesn highresolutionmicrofluidicassayandprobabilisticmodelingrevealcooperationbetweentcellsintumorkilling |