免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:B7-H3 is associated with the armored-cold phenotype and predicts poor immune checkpoint blockade response in melanoma.
B7-H3 is associated with the armored-cold phenotype and predicts poor immune checkpoint blockade response in melanoma.
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黑色素瘤是最适合免疫治疗的肿瘤类型,但并非所有黑色素瘤患者都能对免疫治疗产生应答。B7同源体3(B7-H3)属于B7家族,在多种恶性肿瘤中过表达,但B7-H3在黑色素瘤中的表达模式尚未得到很好的总结。通过使用多个公共数据库,包括癌症基因组图谱(TCGA)、GEPIA和人类蛋白质图谱数据库,研究了B7-H3在黑色素瘤中的表达及其与肿瘤微环境(TME)特征的相关性。
此外,应用本实验室的黑色素瘤组织芯片验证了公共数据库的结果。基于公共队列和本实验室队列,我们发现B7-H3在黑色素瘤肿瘤组织中过表达,且B7-H3高表达与不良临床结局相关。
此外,B7-H3与TIL(肿瘤浸润淋巴细胞)(TILs)水平呈负相关,与胶原浸润呈正相关。具有临床转化价值的是,使用Kaplan-Meier plotter工具检测了B7-H3对常规免疫治疗的预测价值,结果显示B7-H3高表达的黑色素瘤患者对抗PD-1和抗CTLA-4免疫治疗不敏感。
总之,我们首次研究了B7-H3在黑色素瘤中的表达及其与TME特征的相关性,并表明B7-H3是对常规免疫治疗不敏感的黑色素瘤患者中有前景的治疗靶点。
Melanoma is the most suitable tumor type for immunotherapy, but not all melanoma patients could respond to immunotherapy. B7 homolog 3 (B7-H3) belongs to the B7 family and is overexpressed in a number of malignant tumors, but the expression pattern of B7-H3 in melanoma has not been well summarized. The expression of B7-H3 was investigated in melanoma and its correlations with features of the tumor microenvironment (TME) by using various public databases, including the Cancer Genome Atlas (TCGA), the GEPIA, and the Human Protein Atlas databases.
In addition, the in-house melanoma tissue microarray was applied to validate the results from public databases. Based on the public and in-house cohorts, we found that B7-H3 was overexpressed in melanoma tumor tissues and high B7-H3 expression was related to poor clinical outcome.
Moreover, B7-H3 was negatively correlated with levels of tumor-infiltrating lymphocytes (TILs) and positively correlated with collagen infiltration. With clinical translational value, the predictive value of B7-H3 for conventional immunotherapy was detected using the Kaplan-Meier plotter tool, and the results showed that melanoma patients with high B7-H3 expression were insensitive to anti-PD-1 and anti-CTLA-4 immunotherapy.
In conclusion, we first investigate the expression of B7-H3 in melanoma and its correlations with the TME features, and indicate B7-H3 as a promising therapeutic target in melanoma patients that are insensitive to conventional immunotherapy.
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