Asakawa Ayaka, Yoshimoto Ryoto, Kobayashi Maki, Izumi Nanae, Maejima Takanori, Deguchi Tsuneo, Kubota Kazuishi, Takahashi Hisashi, Yamada Miyuki, Ishibashi Sachiko, Onishi Iichiroh, Kinowaki Yuko, Kurata Morito, Kobayashi Masashi, Ishibashi Hironori, Okubo Kenichi, Ohashi Kenichi, Kitagawa Masanobu, Yamamoto Kouhei
Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Molecular Pathology Group, Translational Research Department, Daiichi Sankyo RD Novare, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
Cancers (Basel). 2024 Jun 4;16(11):2140. doi: 10.3390/cancers16112140.
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 CD163PD-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（LSCC）对非小细胞癌的各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）中的表达及意义，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来检测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表达与预后之间的关系，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）表达之间的相关性。肿瘤细胞中高表达B7-H3与较好的预后相关，且CD163⁺PD-L1⁺巨噬细胞数量显著增加。定量分析显示，肿瘤细胞、基质细胞、瘤内肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞中B7-H3与PD-L1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B7-H3表达更高。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，这表明针对B7-H3的疗法可能对PD-L1靶向治疗耐药的患者具有额外疗效。
