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Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer

Most colorectal cancer (CRC) patients present with a microsatellite-stable phenotype, rendering them resistant to immune checkpoint inhibitors (ICIs). Among the contributors to ICI resistance, tumor-derived extracellular vesicles (TEVs) have emerged as critical players. Previously we demonstrated th...

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Autores principales: Gates, Travis J., Wangmo, Dechen, Zhao, Xianda, Subramanian, Subbaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562189/
https://www.ncbi.nlm.nih.gov/pubmed/37822487
http://dx.doi.org/10.1016/j.omto.2023.100727
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author Gates, Travis J.
Wangmo, Dechen
Zhao, Xianda
Subramanian, Subbaya
author_facet Gates, Travis J.
Wangmo, Dechen
Zhao, Xianda
Subramanian, Subbaya
author_sort Gates, Travis J.
collection PubMed
description Most colorectal cancer (CRC) patients present with a microsatellite-stable phenotype, rendering them resistant to immune checkpoint inhibitors (ICIs). Among the contributors to ICI resistance, tumor-derived extracellular vesicles (TEVs) have emerged as critical players. Previously we demonstrated that autologous transfer of TEVs without miR-424 can induce tumor antigen-specific immune responses in CRC models. Therefore, we postulated that allogeneic TEVs, modified to lack miR-424 and derived from an MC38 cells, could induce CD8(+) T cell responses while restraining CT26 cell-based tumor. Here, we show that prophylactic administration of MC38 TEVs, without miR-424, showed a significant augmentation in CD8(+) T-cells within CT26 tumors. This allogenic TEV effect was evident in CT26 tumors but not B16-F10 melanoma. Furthermore, we demonstrated the capacity of dendritic cells (DCs) to internalize TEVs, a possible mechanism to elicit immune response. Our investigation of autologously administered DCs, which had been exposed to modified TEVs, underscores their potential to dampen tumor growth while elevating CD8(+) T cell levels vis-a-vis MC38 wild-type TEVs exposed to DCs. Notably, the modified TEVs were well tolerated and did not increase peripheral blood cytokine levels. Our findings underscore the potential of modified allogeneic TEVs without immune-suppressive factors to elicit robust T cell responses and limit tumor growth.
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spelling pubmed-105621892023-10-11 Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer Gates, Travis J. Wangmo, Dechen Zhao, Xianda Subramanian, Subbaya Mol Ther Oncolytics Original Article Most colorectal cancer (CRC) patients present with a microsatellite-stable phenotype, rendering them resistant to immune checkpoint inhibitors (ICIs). Among the contributors to ICI resistance, tumor-derived extracellular vesicles (TEVs) have emerged as critical players. Previously we demonstrated that autologous transfer of TEVs without miR-424 can induce tumor antigen-specific immune responses in CRC models. Therefore, we postulated that allogeneic TEVs, modified to lack miR-424 and derived from an MC38 cells, could induce CD8(+) T cell responses while restraining CT26 cell-based tumor. Here, we show that prophylactic administration of MC38 TEVs, without miR-424, showed a significant augmentation in CD8(+) T-cells within CT26 tumors. This allogenic TEV effect was evident in CT26 tumors but not B16-F10 melanoma. Furthermore, we demonstrated the capacity of dendritic cells (DCs) to internalize TEVs, a possible mechanism to elicit immune response. Our investigation of autologously administered DCs, which had been exposed to modified TEVs, underscores their potential to dampen tumor growth while elevating CD8(+) T cell levels vis-a-vis MC38 wild-type TEVs exposed to DCs. Notably, the modified TEVs were well tolerated and did not increase peripheral blood cytokine levels. Our findings underscore the potential of modified allogeneic TEVs without immune-suppressive factors to elicit robust T cell responses and limit tumor growth. American Society of Gene & Cell Therapy 2023-09-16 /pmc/articles/PMC10562189/ /pubmed/37822487 http://dx.doi.org/10.1016/j.omto.2023.100727 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Gates, Travis J.
Wangmo, Dechen
Zhao, Xianda
Subramanian, Subbaya
Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title_full Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title_fullStr Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title_full_unstemmed Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title_short Allogeneic tumor cell-derived extracellular vesicles stimulate CD8 T cell response in colorectal cancer
title_sort allogeneic tumor cell-derived extracellular vesicles stimulate cd8 t cell response in colorectal cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562189/
https://www.ncbi.nlm.nih.gov/pubmed/37822487
http://dx.doi.org/10.1016/j.omto.2023.100727
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