Open Access

ARTICLE

Diverse PD-1, CD163, and FOXP3 Profiles in Primary and Metastatic Microenvironments of Prostate Cancer

Ana Clara Ciglioni Salustiano^1,2, Gabriela Barbosa^1,3,4, Rodolfo Borges dos Reis^2,4, Amílcar Castro de Mattos^5,6, Athanase Billis⁶, Leonardo O. Reis^1,3,4,*

1 UroScience, State University of Campinas, Unicamp, Campinas, 13083-875, Brazil
2 Medicine School of Ribeirão Preto, University of São Paulo, Ribeirao Preto, 14049-900, Brazil
3 ImmunOncology, Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, 13034-685, Brazil
4 INCT UroGen, National Institute of Science, Technology and Innovation in Genitourinary Cancer, Campinas, 13083-970, Brazil
5 Pathology Department, Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, 13034-685, Brazil
6 Pathology Department, State University of Campinas, Unicamp, Campinas, 13083-888, Brazil

* Corresponding Author: Leonardo O. Reis. Email:

Oncology Research 2025, 33(11), 3417-3428. https://doi.org/10.32604/or.2025.068023

Received 19 May 2025; Accepted 27 August 2025; Issue published 22 October 2025

Abstract

Objective: The tumor microenvironment plays a pivotal role in prostate cancer progression and may differ across metastatic sites. This study aimed to evaluate and compare the primary and metastatic prostate adenocarcinoma tumor microenvironment. Methods: A total of 27 formalin-fixed paraffin-embedded tissue samples derived from 17 patients diagnosed with prostate adenocarcinoma, including the primary tumors, and the corresponding metastatic lymphatic and hematogenous lesions from various anatomical sites. Immunohistochemical labeling was performed using antibodies against Cluster of Differentiation 3 epsilon chain (CD3e), CD8 alpha chain (CD8a), Cluster of Differentiation 68 (CD68), Cluster of Differentiation 163 (CD163), Forkhead box P3 (FOXP3), Cytotoxic T-Lymphocyte–Associated protein 4 (CTLA-4), B7 homolog 3 (B7-H3), Programmed cell death protein 1 (PD-1), and Marker of proliferation Ki-67 (Ki-67). Comparisons were made between primary and metastatic tumors to assess differences in immune cell infiltration, checkpoint expression, and proliferative indices. Results: Samples were classified into three groups: Primary Tumor n = 12, Lymphatic Metastasis n = 7, and Hematogenous Metastasis n = 10. FOXP3 (p = 0.0017) and CD163 (p = 0.0316) expression levels were significantly higher in the Hematogenous Metastasis compared to both the Primary Tumor and Lymphatic Metastasis. PD-1 showed a clear trend (p = 0.0577) toward higher levels in the Primary Tumor compared to both the Hematogenous Metastasis and Lymphatic Metastasis groups, suggesting distinct immunological landscapes depending on tumor location and progression. Conclusion: Diverse PD-1, CD163, and FOXP3 profiles were observed in primary and metastatic microenvironments of prostate cancer. These findings may contribute to the development of personalized therapeutic strategies and novel prognostic tools beyond conventional histological and TNM staging.

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Supplementary Material

Supplementary Material File

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