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.
肺鳞状细胞癌对多种非小细胞肺癌治疗方案反应不佳，因此需要开发新的治疗策略以改善其预后。尽管针对B7家族分子的免疫疗法已在多种癌症类型中开展研究，但B7-H3在肿瘤微环境中的表达特征、临床意义及其与其他免疫检查点分子的关联尚未得到系统阐释。本研究采用高通量定量多重免疫组化技术检测肿瘤微环境中B7-H3的表达特征，通过回顾性分析110例手术切除病理标本，系统探究B7-H3表达与患者预后的关联及其对肿瘤微环境的影响。在单细胞层面，我们进一步解析了B7-H3与程序性死亡配体-1表达的相关性。研究发现：肿瘤细胞高表达B7-H3与良好预后显著相关，并伴随CD163+PD-L1+巨噬细胞数量的显著增加。定量分析显示，在肿瘤细胞与间质细胞中，以及肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞内，B7-H3与PD-L1表达均呈正相关。与PD-L1阴性细胞相比，具有PD-L1+表型的CD68+细胞、CD163+细胞及CK+细胞均呈现更高的B7-H3表达水平。本研究表明B7-H3与PD-L1在相同细胞中存在表达相关性，提示针对B7-H3的靶向治疗可能为PD-L1靶向治疗耐药患者提供新的治疗选择。
肿瘤(癌症)患者之家