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

Ayaka Asakawa; Ryoto Yoshimoto; Maki Kobayashi; Nanae Izumi; Takanori Maejima; Tsuneo Deguchi; Kazuishi Kubota; Hisashi Takahashi; Miyuki Yamada; Sachiko Ishibashi; Iichiroh Onishi; Yuko Kinowaki; Morito Kurata; Masashi Kobayashi; Hironori Ishibashi; Kenichi Okubo; Kenichi Ohashi; Masanobu Kitagawa; Kouhei Yamamoto

doi:10.3390/cancers16112140

Cancers (Jun 2024)

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

Ayaka Asakawa,
Ryoto Yoshimoto,
Maki Kobayashi,
Nanae Izumi,
Takanori Maejima,
Tsuneo Deguchi,
Kazuishi Kubota,
Hisashi Takahashi,
Miyuki Yamada,
Sachiko Ishibashi,
Iichiroh Onishi,
Yuko Kinowaki,
Morito Kurata,
Masashi Kobayashi,
Hironori Ishibashi,
Kenichi Okubo,
Kenichi Ohashi,
Masanobu Kitagawa,
Kouhei Yamamoto

Affiliations

Ayaka Asakawa: Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Ryoto Yoshimoto: Molecular Pathology Group, Translational Research Department, Daiichi Sankyo RD Novare, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
Maki Kobayashi: Molecular Pathology Group, Translational Research Department, Daiichi Sankyo RD Novare, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
Nanae Izumi: Translational Science Department, Daiichi Sankyo, Inc., Basking Ridge, NJ 07920, USA
Takanori Maejima: Translational Science Department I, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Tsuneo Deguchi: Translational Science Department I, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Kazuishi Kubota: Translational Science Department, Daiichi Sankyo, Inc., Basking Ridge, NJ 07920, USA
Hisashi Takahashi: Molecular Pathology Group, Translational Research Department, Daiichi Sankyo RD Novare, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
Miyuki Yamada: Molecular Pathology Group, Translational Research Department, Daiichi Sankyo RD Novare, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
Sachiko Ishibashi: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Iichiroh Onishi: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Yuko Kinowaki: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Morito Kurata: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Masashi Kobayashi: Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Hironori Ishibashi: Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Kenichi Okubo: Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Kenichi Ohashi: Department of Human Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Masanobu Kitagawa: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Kouhei Yamamoto: Department of Comprehensive Pathology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

DOI: https://doi.org/10.3390/cancers16112140
Journal volume & issue: Vol. 16, no. 11
p. 2140

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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