肿瘤细胞治疗研究
英文原题：The increased co-expression of SLC7A11 and PD-L1 was associated with poor prognosis in extranodal natural killer T-cell lymphoma patients.
我们的研究结果表明，肿瘤细胞特异性共表达 SLC7A11/PD-L1 与结外 NK/T 细胞淋巴瘤（ENKTL）的不良预后相关，提示双靶向治疗可能提高这些患者的疗效。
结外自然杀伤/T细胞淋巴瘤（ENKTL）是一种高度侵袭性的成熟T/NK细胞淋巴瘤，治疗颇具挑战。免疫检查点抑制剂（ICI）虽已在ENKTL中显示临床活性，但原发耐药和应答不持久仍是主要障碍。我们此前发现，天然二萜类化合物kayadiol可通过p53/SLC7A11介导的铁死亡对ENKTL细胞发挥抗肿瘤作用。胱氨酸通过溶质载体家族7成员11（SLC7A11）这一胱氨酸/谷氨酸反向转运体摄取，是谷胱甘肽生物合成的主要调节步骤。为评估SLC7A11在ENKTL中的表达模式，我们对42例新诊断患者的福尔马林固定石蜡包埋（FFPE）标本开展免疫组化分析。结果显示，SLC7A11高表达与总生存期（OS）和无进展生存期（PFS）缩短相关。进一步检测PD-L1发现，SLC7A11与PD-L1表达相关，两者同时高表达也与不良预后相关。为进一步评估肿瘤细胞中SLC7A11和PD-L1的共表达模式，我们开展了荧光多重免疫组化（mIHC）。值得注意的是，SLC7A11和PD-L1均主要定位于CD56+肿瘤细胞。mIHC分析进一步证实，SLC7A11和PD-L1共表达升高与ENKTL患者预后较差相关。在GSE90597队列中对结果进行了外部验证：SLC7A11高表达及其与PD-L1高共表达均与OS较差相关，而单独PD-L1未达统计学显著性。相反，CD8+ PD-1+肿瘤浸润T细胞与临床结局无显著统计学关联。我们的发现表明，肿瘤细胞特异性SLC7A11/PD-L1共表达与ENKTL不良预后相关，提示双靶向治疗可能提高此类患者的疗效。
Extranodal natural killer/T cell lymphoma (ENKTL) is a highly aggressive type of mature T and NK cell lymphoma that faces treatment challenges. Although immune checkpoint inhibitors (ICIs) have shown clinical activity in ENKTL, primary resistance and limited durable responses remain major obstacles. Our previous study demonstrated that the natural diterpenoid compound kayadiol exerted antitumor activity via p53/SLC7A11 mediated ferroptosis in ENKTL cells. Cystine, through the solute carrier family 7 member 11 (SLC7A11)-a cystine/glutamate antiporter-serves as the primary regulator of cystine uptake for glutathione biosynthesis. To evaluate the expression patterns of SLC7A11 in ENKTL, we conducted immunohistochemistry (IHC) analyses on formalin fixed paraffin embedded (FFPE) specimens obtained from 42 newly diagnosed ENKTL patients. The results indicated that high expression of SLC7A11 was associated with decreased overall survival (OS) and progression free survival (PFS). Furthermore, the simultaneous detection of PD L1 expression revealed a correlation between the expressions of SLC7A11 and PD L1, with their mutual high expression also linked to an unfavorable prognosis. To further assess the co expression pattern of SLC7A11 and PD L1 in tumor cells, we performed fluorescent multiplex immunohistochemistry (mIHC). Notably, both SLC7A11 and PD L1 were confirmed to be predominantly localized to CD56 + neoplastic cells. The mIHC analysis further substantiated that elevated co expression of SLC7A11 and PD L1 was associated with a poor prognosis for ENKTL patients. These findings were externally validated in the GSE90597 cohort, where high SLC7A11 expression and high co expression were both associated with poorer OS, whereas PD L1 alone did not reach significance. Conversely, CD8 + PD 1 + tumor infiltrating T cells showed no statistically significant association with clinical outcomes. Our findings demonstrate that tumor cell specific co expression of SLC7A11/PD L1 is associated with a poor prognosis in ENKTL, suggesting that dual targeted therapy may enhance efficacy for these individuals.
MEMBER ACCOUNT
登录成功会直接打开下一页。
