期刊名称：Cancer Cell 
影响因子：44.5
文章题目：Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy
DOI：10.1016/j.ccell.2024.10.008
第一作者：Chen Yang
作者单位：上海交通大学医学院附属仁济医院
引用YOBIBIO产品：U96-3145E  Mouse Cxcl7/nap-2 ELISA Kit 
文献摘要： 
Tumor-initiating cells (TICs) possess the ability to evade anti-tumor immunity, potentially explaining many failures of cancer immunotherapy. Here, we identify CD49f as a prominent marker for discerning TICs in hepatocellular carcinoma (HCC), outperforming other commonly used TIC markers. CD49f-high TICs specifically recruit tumor-promoting neutrophils via the CXCL2-CXCR2 axis and create an immunosuppressive milieu in the tumor microenvironment (TME). Reciprocally, the neutrophils reprogram nearby tumor cells toward a TIC phenotype via secreting CCL4. These cells can evade CD8+ T cell-mediated killing through CCL4/STAT3-induced and CD49f-stabilized CD155 expression. Notably, while aberrant CD155 expression contributes to immune suppression, it also represents a TIC-specific vulnerability. We demonstrate that either CD155 deletion or antibody blockade significantly enhances sensitivity to anti-PD-1 therapy in preclinical HCC models. Our findings reveal a new mechanism of tumor immune evasion and provide a rationale for combining CD155 blockade with anti-PD-1/PD-L1 therapy in HCC.
肿瘤起始细胞 （TIC） 具有逃避抗肿瘤免疫的能力，这可能解释了癌症免疫治疗的许多失败。在这里，我们将 CD49f 确定为肝细胞癌 （HCC） 中识别 TICs 的重要标志物，优于其他常用的 TIC 标志物。CD49f 高 TICs 通过 CXCL2-CXCR2 轴特异性募集促进肿瘤的中性粒细胞，并在肿瘤微环境 （TME） 中产生免疫抑制环境。反相地，中性粒细胞通过分泌 CCL4 将附近的肿瘤细胞重编程为 TIC 表型。这些细胞可以通过 CCL4/STAT3 诱导和 CD49f 稳定的 CD155 表达来逃避 CD8+ T 细胞介导的杀伤。值得注意的是，虽然异常的 CD155 表达有助于免疫抑制，但它也代表了 TIC 特异性的脆弱性。我们证明，在临床前 HCC 模型中，CD155 缺失或抗体阻断显着提高了对抗 PD-1 治疗的敏感性。我们的研究结果揭示了肿瘤免疫逃逸的新机制，并为 CD155 阻断与抗 PD-1/PD-L1 治疗相结合治疗 HCC 提供了理论依据。