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10.1073/pnas.1716266115 http://scihub22266oqcxt.onion/10.1073/pnas.1716266115 C5834689!5834689 !29440406     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29440406 &cmd=llinks): Failed to open stream: HTTP request failed! 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Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity |pdf=|usr=}}{{29440406 }} gab.com Text Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29440406 #FOAvip Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Twit Text FOAVip Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29440406 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29440406 #FOAvip English Wikipedia <ref>{{Cite pmid|29440406 }}</ref> Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity #MMPMID29440406 Davenport AJ ; Cross RS ; Watson KA ; Liao Y ; Shi W ; Prince HM ; Beavis PA ; Trapani JA ; Kershaw MH ; Ritchie DS ; Darcy PK ; Neeson PJ ; Jenkins MR Proc Natl Acad Sci U S A 2018[Feb]; 115 (9 ): E2068-E2076 PMID29440406 show ga Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. |Animals [MESH] |CD3 Complex [MESH] |Cell Adhesion [MESH] |Cell Death [MESH] |Cell Line, Tumor [MESH] |Computational Biology [MESH] |Cytokines/metabolism [MESH] |Dyneins/chemistry [MESH] |Immunological Synapses/*immunology [MESH] |Ligands [MESH] |Lymphocyte Activation [MESH] |Lymphocyte Function-Associated Antigen-1/immunology [MESH] |Mice [MESH] |Microtubules/metabolism [MESH] |Neoplasms/*immunology [MESH] |Receptors, Antigen, T-Cell/*immunology [MESH] |Signal Transduction [MESH]Chimeric antigen receptor T cells form nonclassical and potent immune (epmc).pdf DeepDyve Pubget Overpricing