Patel Vanessa, Corredeira Patrícia, Cavaco Ana, Barroso Tiago, Filipe Pedro, Mansinho André, Abreu Catarina, Szeneszi Lisiana Wachholz, Ribot Julie, Santos Bruno Silva, Costa Luís
Oncology, Unidade Local de Saúde Santa Maria, Lisbon, PRT.
Laboratory, Gulbenkian Institute for Molecular Medicine, Lisbon, PRT.
Cureus. 2025 Mar 16;17(3):e80672. doi: 10.7759/cureus.80672. eCollection 2025 Mar.
Background Prostate cancer (PCa) encompasses a heterogeneous spectrum, ranging from indolent to highly aggressive forms, with approximately 10-20% of patients with initially localized disease later becoming metastatic. Oligometastatic PCa (OMPC) represents an intermediate state between locally advanced and high-volume metastatic disease. Understanding the immune landscape of OMPC and plurimetastatic PCa (PMPC) can provide valuable insights into disease biology, with potential implications for treatment strategies and prognosis. Aim and objective This study aimed to evaluate alterations in circulating immune cell subsets between OMPC and PMPC to identify potential immune biomarkers and therapeutic targets. Methods We conducted a retrospective cohort study of 43 mPC patients. Patients were stratified into two groups based on metastatic spread: OMPC (≤5 metastatic lesions in bone or lymph nodes) and PMPC (>5 lesions and/or visceral involvement). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed via flow cytometry for key immune subsets, including γδ T cells, αβ T cells, and regulatory T cells, with functional assessments performed using cytokine stimulation. Statistical analysis used the Mann-Whitney-Wilcoxon test, with p ≤ 0.05 considered significant. Results OMPC patients exhibited significantly increased γδ2+ T cells compared to PMPC, suggesting enhanced immune surveillance in low metastatic burden. A trend toward elevated γδ2+ T cells expressing interferon-gamma (IFN-γ) was observed in PMPC. No significant differences were observed in other immune subsets. Conclusions γδ2+ T cells represent a distinct immune subset in PCa, potentially influencing disease progression. Despite the small sample size, these findings highlight γδ2+ T cells as promising biomarkers and therapeutic targets. Prospective studies with a larger sample size are warranted to confirm the significance of these findings and explore the mechanistic roles of these cells and possible clinical applications in metastatic PCa (mPC).
背景 前列腺癌（PCa）包含从惰性到高度侵袭性的异质性谱系，约10%-20%初始局限期疾病的患者后来会发生转移。寡转移前列腺癌（OMPC）代表局部晚期和高负荷转移疾病之间的中间状态。了解OMPC和多转移前列腺癌（PMPC）的免疫格局可为疾病生物学提供有价值的见解，对治疗策略和预后具有潜在影响。目的 本研究旨在评估OMPC和PMPC之间循环免疫细胞亚群的变化，以确定潜在的免疫生物标志物和治疗靶点。方法 我们对43例转移性前列腺癌（mPC）患者进行了一项回顾性队列研究。根据转移扩散情况将患者分为两组：OMPC（骨或淋巴结转移灶≤5个）和PMPC（>5个病灶和/或内脏受累）。分离外周血单个核细胞（PBMC），通过流式细胞术分析关键免疫亚群，包括γδ T细胞、αβ T细胞和调节性T细胞，并使用细胞因子刺激进行功能评估。统计分析采用Mann-Whitney-Wilcoxon检验，p≤0.05认为具有统计学意义。结果 与PMPC相比，OMPC患者的γδ2+ T细胞显著增加，表明低转移负荷下免疫监视增强。在PMPC中观察到表达干扰素-γ（IFN-γ）的γδ2+ T细胞有升高趋势。其他免疫亚群未观察到显著差异。结论 γδ2+ T细胞是PCa中一个独特的免疫亚群，可能影响疾病进展。尽管样本量较小，但这些发现突出了γδ2+ T细胞作为有前景的生物标志物和治疗靶点。有必要进行更大样本量的前瞻性研究，以证实这些发现的意义，并探索这些细胞的机制作用以及在转移性前列腺癌（mPC）中的可能临床应用。
