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

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.

journal_name

Eur J Immunol

authors

Alotaibi F,Rytelewski M,Figueredo R,Zareardalan R,Zhang M,Ferguson PJ,Maleki Vareki S,Najajreh Y,El-Hajjar M,Zheng X,Min WP,Koropatnick J

doi

10.1002/eji.201948309

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

695-704

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

50

pub_type

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