The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer
The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272918/full |
| _version_ | 1797384897879343104 |
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| author | Kaito A. Hioki Kaito A. Hioki Daniel J. Ryan Iris Thesmar Adam C. Lynch Leonid A. Pobezinsky Elena L. Pobezinskaya |
| author_facet | Kaito A. Hioki Kaito A. Hioki Daniel J. Ryan Iris Thesmar Adam C. Lynch Leonid A. Pobezinsky Elena L. Pobezinskaya |
| author_sort | Kaito A. Hioki |
| collection | DOAJ |
| description | The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the “mosquito effect”. |
| first_indexed | 2024-03-08T21:46:14Z |
| format | Article |
| id | doaj.art-a8da7881315c4b56b8e0abab54cb6f54 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T21:46:14Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a8da7881315c4b56b8e0abab54cb6f542023-12-20T08:58:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12729181272918The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transferKaito A. Hioki0Kaito A. Hioki1Daniel J. Ryan2Iris Thesmar3Adam C. Lynch4Leonid A. Pobezinsky5Elena L. Pobezinskaya6Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesUMass Biotech Training Program (BTP), University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesDepartment of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United StatesThe phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the “mosquito effect”.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272918/fullintercellular transfertumorTregsCD8 T cellscytoplasmexhaustion |
| spellingShingle | Kaito A. Hioki Kaito A. Hioki Daniel J. Ryan Iris Thesmar Adam C. Lynch Leonid A. Pobezinsky Elena L. Pobezinskaya The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer Frontiers in Immunology intercellular transfer tumor Tregs CD8 T cells cytoplasm exhaustion |
| title | The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| title_full | The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| title_fullStr | The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| title_full_unstemmed | The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| title_short | The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| title_sort | mosquito effect regulatory and effector t cells acquire cytoplasmic material from tumor cells through intercellular transfer |
| topic | intercellular transfer tumor Tregs CD8 T cells cytoplasm exhaustion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272918/full |
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