CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.
The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.
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肺鳞状细胞癌(LSCC)对非小细胞癌的多种治疗均具有耐药性;因此,需要新的治疗方法来改善LSCC的预后。尽管针对B7家族分子的免疫治疗已被探索用于多种癌症类型的治疗,但B7-H3在肿瘤微环境(TME)中的表达及意义及其与其他免疫检查点分子的关系尚未被详细研究。
我们采用高通量多重定量免疫组化检测TME中B7-H3的表达。我们回顾性分析了110例手术切除的病理标本,研究了B7-H3表达与预后的关系以及B7-H3表达对TME的影响。
我们检测了单细胞中B7-H3与程序性细胞死亡配体1(PD-L1)表达的相关性。肿瘤细胞中B7-H3高表达与更好的预后及CD163 + PD-L1 + 巨噬细胞数量的显著增加相关。定量分析显示,肿瘤细胞和基质细胞中B7-H3与PD-L1表达呈正相关,同一细胞中的瘤内TIL(肿瘤浸润淋巴细胞)和肿瘤相关巨噬细胞中亦呈正相关。具有PD-L1 + 表型的CD68 +、CD163 + 和CK + 细胞相比PD-L1 - 细胞具有更高的B7-H3表达。
我们的研究结果表明,同一细胞中B7-H3与PD-L1表达存在相关性,提示靶向B7-H3的治疗可能为对PD-L1靶向治疗耐药的患者提供额外的疗效。
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail.
We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME.
We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively.
We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163 + PD-L1 + macrophages.
Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68 + , CD163 + , and CK + cells with PD-L1 + phenotypes had higher B7-H3 expression compared to PD-L1 - cells.
Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.
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