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A multilayered blood vessel/tumor tissue chip to investigate T cell infiltration into solid tumor tissues
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jaehyun | - |
dc.contributor.author | Kim, Seong-Eun | - |
dc.contributor.author | Moon, Dowon | - |
dc.contributor.author | Doh, Junsang | - |
dc.date.accessioned | 2024-05-16T01:21:38Z | - |
dc.date.available | 2024-05-16T01:21:38Z | - |
dc.date.created | 2021-07-09 | - |
dc.date.created | 2021-07-09 | - |
dc.date.issued | 2021-06-07 | - |
dc.identifier.citation | Lab on a Chip - Miniaturisation for Chemistry and Biology, Vol.21 No.11, pp.2142-2152 | - |
dc.identifier.issn | 1473-0197 | - |
dc.identifier.uri | https://hdl.handle.net/10371/202458 | - |
dc.description.abstract | Cancer immunotherapies based on the ability of T cells to recognize and kill tumor cells (TCs), including immune checkpoint blockade (ICB) therapy and chimeric antigen receptor (CAR) T cell therapy, have been greatly successful recently, but they are applicable for only a fraction of patients. One of the main challenges in cancer immunotherapy is the improvement of T cell infiltration into solid tumor tissues, as T cells can exert cytotoxicity against TCs only when they are in contact with TCs. T cells in the bloodstream infiltrate into solid tumor tissues by following two steps known as extravasation and interstitial migration. Herein, we developed a multilayered blood vessel/tumor tissue chip (MBTC) that allows systematic investigation on T cell tumor infiltration. The MBTC is composed of a top fluidic chamber, a porous membrane covered with an endothelial cell (EC) monolayer, and a collagen gel block encapsulating TCs. The full sequence of T cell tumor infiltration, including extravasation and interstitial migration, required for TC killing is demonstrated in the MBTCs: T cells applied through the top fluidic chamber of the MBTCs exhibited dynamic interactions with ECs for extravasation, including intraluminal crawling and transendothelial migration (TEM). After extravasation, T cells migrate toward TCs located at the bottom of a collagen block to kill them. Key characteristics of T cell dynamics in tumor microenvironments are recapitulated in the MBTCs: the vascular endothelial growth factor (VEGF) produced by TCs suppressed EC activation by inflammatory cytokines, or induced EC anergy, thereby significantly reducing T cell extravasation, whereas chemokines produced by TCs triggered T cell chemotaxis toward TCs. Anti-VEGF treatment in the MBTCs reverts EC anergy and promotes T cell infiltration, similar to the clinical effects of anti-VEGF. The MBTC is a useful model for pre-clinical evaluation of immunotherapeutics and the fundamental study of tumor immunology. | - |
dc.language | 영어 | - |
dc.publisher | Royal Society of Chemistry | - |
dc.title | A multilayered blood vessel/tumor tissue chip to investigate T cell infiltration into solid tumor tissues | - |
dc.type | Article | - |
dc.identifier.doi | 10.1039/d1lc00182e | - |
dc.citation.journaltitle | Lab on a Chip - Miniaturisation for Chemistry and Biology | - |
dc.identifier.wosid | 000645230800001 | - |
dc.identifier.scopusid | 2-s2.0-85107410900 | - |
dc.citation.endpage | 2152 | - |
dc.citation.number | 11 | - |
dc.citation.startpage | 2142 | - |
dc.citation.volume | 21 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Doh, Junsang | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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