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

被引：3

作者：

Asakawa, Ayaka ^{[1
]}

Yoshimoto, Ryoto ^{[2
]}

Kobayashi, Maki ^{[2
]}

Izumi, Nanae ^{[3
]}

Maejima, Takanori ^{[4
]}

Deguchi, Tsuneo ^{[4
]}

Kubota, Kazuishi ^{[3
]}

Takahashi, Hisashi ^{[2
]}

Yamada, Miyuki ^{[2
]}

Ishibashi, Sachiko ^{[5
]}

Onishi, Iichiroh ^{[5
]}

Kinowaki, Yuko ^{[5
]}

Kurata, Morito ^{[5
]}

Kobayashi, Masashi ^{[1
]}

Ishibashi, Hironori ^{[1
]}

Okubo, Kenichi ^{[1
]}

Ohashi, Kenichi ^{[6
]}

Kitagawa, Masanobu ^{[5
]}

Yamamoto, Kouhei ^{[5
,6
]}

机构：

[1] Tokyo Med & Dent Univ, Dept Thorac Surg, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan

[2] Daiichi Sankyo RD Novare, Mol Pathol Grp, Translat Res Dept, 1-16-13 Kitakasai,Edogawa Ku, Tokyo 1348630, Japan

[3] Daiichi Sankyo Inc, Translat Sci Dept, Basking Ridge, NJ 07920 USA

[4] Daiichi Sankyo Co Ltd, Translat Sci Dept 1, 1-2-58 Hiromachi,Shinagawa Ku, Tokyo 1408710, Japan

[5] Tokyo Med & Dent Univ, Grad Sch Med & Dent, Dept Comprehens Pathol, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan

[6] Tokyo Med & Dent Univ, Grad Sch Med & Dent, Dept Human Pathol, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138510, Japan

来源：

CANCERS | 2024年 / 16卷 / 11期

关键词：

lung squamous cell cancer; B7-H3; PD-L1; multiplex immunohistochemistry; tumor microenvironment; POOR-PROGNOSIS; IMMUNE; CANCER; CHECKPOINTS; PD-L1; CD276;

D O I：

10.3390/cancers16112140

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer. 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. 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. The correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells was also examined. A quantitative analysis of protein expression in macrophages and cancer cells revealed that PD-L1-positive cells expressed higher levels of B7-H3 than that of PD-L1-negative 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.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.

引用

页数：14

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