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Open Access Article Issue
Diverse PD-1, CD163, and FOXP3 Profiles in Primary and Metastatic Microenvironments of Prostate Cancer
Oncology Research 2025, 33(11): 3417-3428
Published: 22 October 2025
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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.

Open Access Article Issue
Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial
Oncology Research 2025, 33(6): 1495-1503
Published: 29 May 2025
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Objective

To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG.

Methods

Phase 1 and mechanistic longitudinal, prospective, single-blind randomized study (NCT04806178). Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor (TURBT) in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo (0.9% saline) administered 15 days before the start of intravesical BCG therapy. Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene (IFITM3), Interleukin 1 beta (IL1-BETA), interleukin-2 receptor alpha chain (IL2 RA), Interleukin 6 (IL 6), Interleukin 10 (IL 10), Tumor necrosis factor alpha (TNF-α), Interferon-β, AXL, and one protease CASPASE 8.

Results

After 1 exclusion, twenty patients were randomized to intradermal BCG (n = 11) and intradermal placebo (n = 9). There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy, and no difference in the expression of the cytokines and proteases analyzed between control and intervention, and over time.

Conclusions

Intradermal BCG administration before intravesical application was safe, with no increase in adverse effects. It also does not seem to change the analyzed targets during the intravesical induction-phase BCG. Other immune targets should be explored in the future. The Brazilian tuberculosis-endemic status, where BCG vaccination is mandatory, might have affected the results.

Open Access Article Issue
Prostate cancer temporal and regional trends in Brazil
Oncology Research 2024, 32(10): 1565-1573
Published: 18 September 2024
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Objectives

The Brazilian Unified Health System (Sistema Único de Saúde−SUS) is the universal public healthcare system of Brazil that maintains a nationwide database of its patients. Our primary objective was to analyze regional and temporal trends, while our secondary goal was to establish correlations between states’ health economy status and their prostate cancer (PCa) epidemiology.

Methods

We analyzed Brazil’s nationwide data on prostate cancer (PCa) incidence, mortality, and care gathered between 2013 and 2021 by the Information Technology Department of SUS (DATA-SUS), updated monthly using the International Classification of Diseases (ICD-10) code.

Results

In the period, 273,933 new cases of PCa and 135,336 PCa deaths were reported in men aged 50 years or over in Brazil. The median annual PCa-specific incidence rate (PCSIR) ranged from 14.7 in the Southeast to 6.9 in the North region and the median annual PCa-specific mortality rate (PCSMR) ranged from 7.7 in the Northeast to 6.0 in the South region (per 10,000 men >50). The median annual mortality to incidence ratio (MIR) was highest in the North (0.88) and lowest in the Southeast region (0.44). There were significant regional differences in PCa treatment rates (per new cases); the Midwest region had the highest median annual surgery rate (0.63) while the North region had the highest median annual systemic therapy rate (0.75) and the lowest radiation therapy rate (0.06). Temporal analysis of the data showed significant change in annual rate trends after the year 2018 for PCSIR (coefficient [β] = +3.66, p < 0.001), any treatment (β = −0.06, p = 0.016), surgery ([SR] β = +0.05, p = 0.017) radiation therapy ([RTR] β = −0.06, p = 0.005) and systemic therapy ([STR] β = −0.10, p = 0.002). After the 2020 pandemic, annual PCSIR decreased (β = −2.15, p = 0.002) but annual PCSMR, MIR, and treatment rates remained stable. Correlation studies showed that the PCSIR was strongly negatively correlated with STR (p < 0.001) and positively correlated with RTR (p = 0.004). MIR was positively correlated with STR (p < 0.001) and negatively correlated with the number of robotic surgical systems per million population (p = 0.003).

Conclusion

Our data shows that PCa care is dependent on the region and is likely influenced by access to treatment options. Furthermore, changes after the year 2018 underscore the influence of international guidelines on Brazilian clinicians’ decision-making especially concerning population screening which in turn affected incidence and treatment rates. Limitation of our study includes limited patient-related information and data on private practices as well as an unknown impact of traveling patients.

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