Targeting CD47 in Sezary syndrome with SIRPαFc
Targeting CD47 in Sezary syndrome with SIRPαFc
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DOI：
10.1182/bloodadvances.2018030577
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发表时间：
2019-04-09
期刊：
影响因子：
7.5
通讯作者：
Akilov, Oleg E.
中科院分区：
文献类型：
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作者：
Johnson, Lisa D. S.;Banerjee, Swati;Akilov, Oleg E.
Sezary综合征（SS）是皮肤T细胞淋巴瘤的白血病变体，其治疗选择有限且很少发生长期缓解，因此需要研究新的治疗方法。CD 47已成为多种肿瘤类型的有希望的靶点，但其在SS中的作用仍不清楚。在这里，我们表明，CD 47是高表达的Sezary细胞在外周血和皮肤，和高水平的CD 47表达与SS患者的总生存期（OS）较差。我们还表明，CD 47的表达Sezary细胞的白细胞介素4（IL-4），IL-7，IL-13的影响下。信号调节蛋白α Fc（SIRP α Fc; TTI-621）是一种新型CD 47诱饵受体，可触发巨噬细胞介导的Sezary细胞吞噬作用，当在临床试验环境中给药时，可显著降低肿瘤负荷。我们得出结论，抑制CD 47-SIRP α信号通路对SS患者具有治疗益处。
Sezary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma, has limited treatment options and rare occurrences of long-term remission, thus warranting research into new treatment approaches. CD47 has emerged as a promising target for multiple tumor types, but its role in SS remains unknown. Here, we show that CD47 is highly expressed on Sezary cells in the peripheral blood and skin, and the high level of CD47 expression correlates with worse overall survival (OS) in patients with SS. We also demonstrate that CD47 expression on Sezary cells is under the influence of interleukin 4 (IL-4), IL-7, and IL-13. Signal regulatory protein alpha Fc (SIRP alpha Fc; TTI-621), a novel CD47 decoy receptor, triggers macrophage-mediated phagocytosis of Sezary cells and, when administered in clinical trial settings, results in significant tumor load reduction. We conclude that inhibition of the CD47-SIRP alpha signaling pathway has therapeutic benefit for patients with SS.