下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Programmed Cell Death Ligand-1 (PDL-1) Correlates With Tumor Infiltration by Immune Cells and Represents a Promising Target for Immunotherapy in Endometrial Cancer.
在EC中,PD-L1表达无预后意义,但与其他致癌因素相关,并提示肿瘤中免疫细胞浸润增加。因此,PD-1/PD-L1免疫检查点阻断似乎非常有前景,至少在部分EC患者中如此。
子宫内膜癌(EC)是西半球最常见的妇科癌症之一。然而,合适的治疗选择仍然不足,尤其是对于晚期阶段。免疫检查点阻断通过抑制免疫检查点因子程序性细胞死亡-1(PD-1)和程序性细胞死亡配体-1(PD-L1)的免疫抑制活性,代表了一种有前景的替代已确立的癌症疗法的方法。在本研究中,我们表征了生物标志物PD-L1表达在EC中的临床相关性及其预后能力。
对87例EC患者的肿瘤组织样本进行了回顾性免疫组化分析(PD-L1、p16、雌激素受体、孕激素受体、HER2/neu、Ki-67、CD3、CD20、CD68)。
17.3%的EC患者为PD-L1阳性。PD-L1状态并非EC的合适预后标志物,但与T3/T4分期、淋巴结阳性状态、p16表达以及雌激素和孕激素受体缺失相关。PD-L1阳性组织显示淋巴细胞、单核细胞和巨噬细胞浸润增加,尽管并非在所有情况下均具有统计学显著性。
BACKGROUND/AIM: Endometrial carcinoma (EC) is one of the most common gynecological cancers in the Western Hemisphere. Nevertheless, there are not enough appropriate treatment options, especially for advanced stages. The immune checkpoint blockade represents a promising alternative to established cancer therapies by suppressing the immune-inhibitory activity of the immune checkpoint factors programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In the present study, we characterized the clinical relevance of the biomarker PD-L1 expression in terms of its prognostic capabilities in EC. PATIENTS AND METHODS: Tumor tissue samples from 87 EC patients were retrospectively analyzed by immunohistochemistry (PD-L1, p16, estrogen receptor, progesterone receptor, HER2/neu, Ki-67, CD3, CD20, CD68). RESULTS: A total of 17.3% of EC patients were PD-L1 positive. PD-L1 status did not represent a suitable prognostic marker in EC, but correlated with T3/T4stage, positive lymph node status, p16 expression, and absence of estrogen and progesterone receptor. PD-L1 positive tissues showed increased infiltration with lymphocytes, monocytes, and macrophages, although not statistically significant in every case. CONCLUSION: In EC, PD-L1 expression has no prognostic significance, but correlates with other oncogenic factors and indicates increased infiltration of the tumor with immune cells. Thus, PD-1/PD-L1 immunecheckpoint blockade seems to be very promising, at least in a subset of EC patients.
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