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The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma:
Ayaka Asakawa1, Ryoto Yoshimoto2, Maki Kobayashi2
1Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
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.
Insights
New research on lung squamous cell carcinoma (LSCC) reveals B7-H3 expression correlates with better prognosis and PD-L1. Targeting B7-H3 may benefit patients resistant to PD-L1 therapies.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- Lung squamous cell carcinoma (LSCC) presents a therapeutic challenge for non-small cell lung cancer.
- Novel therapeutic strategies are crucial for improving LSCC patient outcomes.
- The role of B7-H3 in the tumor microenvironment (TME) and its interplay with immune checkpoints in LSCC remain underexplored.
Purpose of the Study:
- To investigate the expression and prognostic significance of B7-H3 in the LSCC tumor microenvironment.
- To explore the relationship between B7-H3 and other immune checkpoint molecules, specifically programmed cell death-ligand 1 (PD-L1).
- To assess the potential of B7-H3 as a therapeutic target in LSCC.
Main Methods:
- Utilized high-throughput quantitative multiplex immunohistochemistry on 110 retrospectively collected LSCC pathological specimens.
- Examined B7-H3 expression in tumor cells and the TME.
- Assessed the correlation between B7-H3 and PD-L1 expression at the single-cell level.
Main Results:
- High B7-H3 expression in tumor cells was linked to a better prognosis in LSCC patients.
- Increased B7-H3 expression correlated with a higher number of CD163+PD-L1+ macrophages in the TME.
- A positive correlation was observed between B7-H3 and PD-L1 expression within the same tumor and stromal cells, including immune cells.
Conclusions:
- B7-H3 expression is associated with improved prognosis and specific immune cell infiltration patterns in LSCC.
- A direct correlation exists between B7-H3 and PD-L1 expression in various cell types within the LSCC TME.
- Targeting B7-H3 may offer a promising therapeutic avenue for LSCC patients who are refractory to current PD-L1-based immunotherapies.
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