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

作者：Faizah Alotaibi, Mateusz Rytelewski, René Figueredo, Ronak Zareardalan, Meng Zhang, Peter J. Ferguson, Saman Maleki Vareki, Yousef Najajreh, Mikal El‐Hajjar, Xiufen Zheng, Wei‐Ping Min, James Koropatnick · 发表于：European Journal of Immunology · 年份：2020 · DOI：10.1002/eji.201948309 · 被引用次数：44 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Abstract CD5 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.