CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity

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dc.contributor.authorAlotaibi, Faizah
dc.contributor.authorRytelewski, Mateusz
dc.contributor.authorFigueredo, Rene
dc.contributor.authorZareardalan, Ronak
dc.contributor.authorZhang, Meng
dc.contributor.authorFerguson, Peter J
dc.contributor.authorVareki, Saman Maleki
dc.contributor.authorNajajreh, Yousef
dc.contributor.authorEl-Hajjar, Mikal
dc.contributor.authorZheng, Xiufen
dc.contributor.authorMin, Wei-ping
dc.contributor.authorKoropatnick, James
dc.date.accessioned2020-07-21T10:24:15Z
dc.date.available2020-07-21T10:24:15Z
dc.date.issued2020-01-15
dc.description.abstractCD5 is expressed on T cells and a subset of B cells (B1a). It can attenuate TCR signalling and impair CTL activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti‐tumour activity against tumours (including solid tumours) has not been explored. CD5 knockout mice show increased anti‐tumour immunity: reducing CD5 on CTLs may be therapeutically beneficial to enhance the anti‐tumour response. Here, we show that ex vivo administration of a function‐blocking anti‐CD5 MAb to primary mouse CTLs of both tumour‐naïve mice and mice bearing murine 4T1 breast tumour homografts enhanced their capacity to respond to activation by treatment with anti‐CD3/anti‐CD28 MAbs or 4T1 tumour cell lysates. Furthermore, it enhanced TCR signalling (ERK activation) and increased markers of T cell activation, including proliferation, CD69 levels, IFN‐γ production, apoptosis and Fas receptor and Fas ligand levels. Finally, CD5 function‐blocking MAb treatment enhanced the capacity of CD8+ T cells to kill 4T1‐mouse tumour cells in an ex vivo assay. These data support the potential of blockade of CD5 function to enhance T cell‐mediated anti‐tumour immunity.en_US
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/5696
dc.language.isoenen_US
dc.titleCD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicityen_US
dc.typeArticleen_US
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