The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study

Cancers Pub Date : 2024-06-04 DOI:10.3390/cancers16112140
A. Asakawa, Ryoto Yoshimoto, Maki Kobayashi, Nanae Izumi, Takanori Maejima, Tsuneo Deguchi, K. Kubota, H. Takahashi, Miyuki Yamada, S. Ishibashi, Iichiroh Onishi, Yuko Kinowaki, Morita Kurata, Masashi Kobayashi, H. Ishibashi, Kenichi Okubo, Kenichi Ohashi, Masanobu Kitagawa, Kouhei Yamamoto
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Abstract

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.
肺鳞癌肿瘤微环境中 B7-H3 表达的综合特征:一项回顾性研究
肺鳞状细胞癌(LSCC)对非小细胞癌的各种疗法均难治,因此需要新的治疗方法来改善 LSCC 的预后。虽然针对 B7 家族分子的免疫疗法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)中的表达和意义及其与其他免疫检查点分子的关系尚未得到详细研究。我们使用高通量定量多重免疫组化技术检测了 B7-H3 在肿瘤微环境中的表达。我们利用 110 例手术切除的病理标本,回顾性地研究了 B7-H3 表达与预后之间的关系,以及 TME 中 B7-H3 表达的变化。我们研究了B7-H3与单细胞中程序性细胞死亡配体1(PD-L1)表达之间的相关性。肿瘤细胞中 B7-H3 的高表达与较好的预后和 CD163+PD-L1+ 巨噬细胞数量的显著增加有关。定量分析显示,B7-H3 和 PD-L1 在肿瘤细胞和基质细胞以及瘤内肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞中的表达呈正相关。与 PD-L1- 细胞相比,具有 PD-L1+ 表型的 CD68+、CD163+ 和 CK+ 细胞具有更高的 B7-H3 表达。我们的研究结果表明,B7-H3和PD-L1在相同细胞中的表达存在相关性,这表明针对B7-H3的疗法可为PD-L1靶向疗法难治性患者带来额外疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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