CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity. Issue 5 (25th February 2020)

• Record Type: Journal Article
• Authors: Alotaibi, Faizah; Rytelewski, Mateusz; Figueredo, Rene; Zareardalan, Ronak; Zhang, Meng; Ferguson, Peter J; Maleki Vareki, Saman; Najajreh, Yousef; El‐Hajjar, Mikal; Zheng, Xiufen; Min, Wei‐ping; Koropatnick, James
• Is Part Of: European journal of immunology. Volume 50:Issue 5(2020)
• Page Start: 695
• Page End: 704
• Publication Date: 2020-02-25
• Subjects: AICD -- Anti‐tumour immunity -- CD5 -- CD8+ T cell -- Fas receptor; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948309
• Languages: English
• ISSNs: 0014-2980

Abstract

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. Abstract : MHC‐TCR interaction leads to T cell activation, but CD5 expression in the immunological synapse attenuates it. Functional blockade of CD5 will then enhance T cell activation and anti‐tumour function.