Exploratory Immunohistochemical Profiling of FOXP3, PD-1 and CD32B in Resectable Lung Adenocarcinoma

<b>Background:</b> Regulatory T cells (FOXP3<sup>+</sup>), checkpoint signaling (PD-1), and inhibitory B-cell signaling (CD32B/FCGR2B) may shape recurrence risk after resection of lung adenocarcinoma, but small, stage-heterogeneous cohorts complicate inference. <b>Methods:</b> We profiled 21 resected lung adenocarcinomas by immunohistochemistry (IHC) for CD3, CD8, FOXP3, PD-1, CD19, and CD32B. Five systematically sampled 200× fields per stain were quantified in ImageJ to derive continuous percentages and prespecified ratios: FOXP3/CD8 and CD32B/CD19 (primary), and PD-1/CD8 (exploratory). Analyses emphasized effect sizes with exact non-parametric tests for clinicopathologic associations and Cox time-to-event models for disease-free survival (DFS). Kaplan-Meier plots used median splits for visualization only. <b>Results:</b> Higher immunosuppressive balance associated with adverse features and shorter DFS. Patients with higher FOXP3/CD8 and CD32B/CD19 had markedly shorter DFS on K-M displays (FOXP3/CD8: 18.9 vs. 45.6 months; CD32B/CD19: 25.0 vs. 72.8 months). In Cox models, each ratio was associated with increased hazard of recurrence (FOXP3+PD-1/CD8, HR 2.03, 95% CI 1.26-3.29; CD32B/CD19, HR 1.98, 95% CI 1.16-3.37). <b>Conclusions:</b> In this hypothesis-generating pilot, an immunosuppressive tumor microenvironment, indexed by higher FOXP3 (relative to CD8) and higher CD32B (relative to CD19), portends earlier recurrence after surgery. These results support external validation in larger, stage-balanced cohorts and motivate incorporation of quantitative IHC ratios into postoperative risk stratification.

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Journal
Cancers
Published
2025-12-04
DOI
https://doi.org/10.3390/cancers17233886
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00

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article

Exploratory Immunohistochemical Profiling of FOXP3, PD-1 and CD32B in Resectable Lung Adenocarcinoma

Kuan-Hsun Lian, Chung‐Yu Chen, Yu‐Ting Tseng, Long-Wei Lin et al.
Cancers
Cancer Immunotherapy and Biomarkers
article

Exploratory Immunohistochemical Profiling of FOXP3, PD-1 and CD32B in Resectable Lung Adenocarcinoma

Kuan-Hsun Lian, Chung‐Yu Chen, Yu‐Ting Tseng, Long-Wei Lin, H.C. Chuang
article en

Abstract

<b>Background:</b> Regulatory T cells (FOXP3<sup>+</sup>), checkpoint signaling (PD-1), and inhibitory B-cell signaling (CD32B/FCGR2B) may shape recurrence risk after resection of lung adenocarcinoma, but small, stage-heterogeneous cohorts complicate inference. <b>Methods:</b> We profiled 21 resected lung adenocarcinomas by immunohistochemistry (IHC) for CD3, CD8, FOXP3, PD-1, CD19, and CD32B. Five systematically sampled 200× fields per stain were quantified in ImageJ to derive continuous percentages and prespecified ratios: FOXP3/CD8 and CD32B/CD19 (primary), and PD-1/CD8 (exploratory). Analyses emphasized effect sizes with exact non-parametric tests for clinicopathologic associations and Cox time-to-event models for disease-free survival (DFS). Kaplan-Meier plots used median splits for visualization only. <b>Results:</b> Higher immunosuppressive balance associated with adverse features and shorter DFS. Patients with higher FOXP3/CD8 and CD32B/CD19 had markedly shorter DFS on K-M displays (FOXP3/CD8: 18.9 vs. 45.6 months; CD32B/CD19: 25.0 vs. 72.8 months). In Cox models, each ratio was associated with increased hazard of recurrence (FOXP3+PD-1/CD8, HR 2.03, 95% CI 1.26-3.29; CD32B/CD19, HR 1.98, 95% CI 1.16-3.37). <b>Conclusions:</b> In this hypothesis-generating pilot, an immunosuppressive tumor microenvironment, indexed by higher FOXP3 (relative to CD8) and higher CD32B (relative to CD19), portends earlier recurrence after surgery. These results support external validation in larger, stage-balanced cohorts and motivate incorporation of quantitative IHC ratios into postoperative risk stratification.

CancersVol. 17(23)
National Taiwan University (TW), National Taiwan University Hospital (TW), National Yunlin University of Science and Technology (TW)
National Taiwan University Hospital, National Taiwan University, National Taiwan University Hospital Yunlin Branch
Openalex Percentile: Top 47%
Cancer Immunotherapy and Biomarkers
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