CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity.,European Journal of Immunology

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CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-02-25 , DOI: 10.1002/eji.201948309
Faizah Alotaibi _{1,

2} , Mateusz Rytelewski ₃ , Rene Figueredo ₄ , Ronak Zareardalan ₂ , Meng Zhang ₅ , Peter J Ferguson ₂ , Saman Maleki Vareki _{2,

4} , Yousef Najajreh ₆ , Mikal El-Hajjar _{1,

2} , Xiufen Zheng ₄ , Wei-Ping Min _{4,

5} , James Koropatnick _{1,

2,

4}

Affiliation

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.

中文翻译：

CD5阻断增强了离体CD8 + T细胞的活化和肿瘤细胞的细胞毒性。

CD5在T细胞和B细胞的一个子集（B1a）中表达。它可以减弱TCR信号传导并损害CTL活化，是在白血病T细胞和B细胞上表达的可治疗的靶向肿瘤抗原。然而，尚未探索功能性阻断CD5以增加针对肿瘤（包括实体瘤）的T细胞抗肿瘤活性的潜在治疗作用。CD5基因敲除小鼠显示出增强的抗肿瘤免疫力：减少CTL上的CD5可能在治疗上有益于增强抗肿瘤反应。在这里，我们表明，对未接受过瘤的小鼠和携带鼠4T1乳腺肿瘤同种移植物的小鼠的原代小鼠CTL进行功能阻断性抗CD5 MAb的离体给药，可增强它们通过用抗CD3 / anti -CD28 MAb或4T1肿瘤细胞裂解物。此外，它增强了TCR信号传导（ERK激活）并增加了T细胞激活的标志物，包括增殖，CD69水平，IFN-γ产生，细胞凋亡以及Fas受体和Fas配体水平。最后，在离体测定中，CD5功能阻断性单克隆抗体治疗增强了CD8 + T细胞杀死4T1小鼠肿瘤细胞的能力。这些数据支持了CD5功能增强T细胞介导的抗肿瘤免疫力的潜力。

更新日期：2020-02-25

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