XPO1 (Exportin-1/CRM1) 是一种核输出蛋白，在癌症中经常过度表达，并作为肿瘤发生的驱动因素。目前，针对 XPO1 的小分子正在临床上用作抗癌药物。我们将 XPO1 确定为自然杀伤 (NK) 细胞的靶标。利用免疫肽组学，我们鉴定了一种源自 XPO1 的肽，它可以在人类白细胞抗原 C 的背景下被激活的 NK 细胞受体 KIR2DS2 识别。该肽可以经过内源性加工并呈递，通过该受体特异性激活 NK 细胞。尽管癌症中 XPO1 的高表达通常与不良预后相关，但我们表明，如果有 NK 细胞浸润的伴随证据，特定癌症（例如肝细胞癌）的结果可以得到显着改善。因此，我们将 XPO1 确定为 NK 细胞识别的真正肿瘤抗原，这为实体瘤的 NK 细胞治疗的个性化方法提供了机会。

XPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells. Using immunopeptidomics, we have identified a peptide derived from XPO1 that can be recognized by the activating NK cell receptor KIR2DS2 in the context of human leukocyte antigen-C. The peptide can be endogenously processed and presented to activate NK cells specifically through this receptor. Although high XPO1 expression in cancer is commonly associated with a poor prognosis, we show that the outcome of specific cancers, such as hepatocellular carcinoma, can be substantially improved if there is concomitant evidence of NK cell infiltration. We thus identify XPO1 as a bona fide tumor antigen recognized by NK cells that offers an opportunity for a personalized approach to NK cell therapy for solid tumors.