Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), CP-6109, Campinas, São Paulo, 13083-865, Brazil.
Ovarian Cancer Research Group, Obstetrics & Gynecology Department, University of British Columbia, Vancouver, BC, V6Z 2K8, Canada.
Med Oncol. 2024 Oct 15;41(11):287. doi: 10.1007/s12032-024-02533-z.
Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8 T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.
非肌肉浸润性膀胱癌（NMIBC）由于其高复发率和复杂的肿瘤微环境（TME），给治疗带来了挑战。本研究探讨了 OncoTherad®（MRB-CFI1）纳米免疫疗法对卡介苗无反应性 NMIBC 的 TME 的影响，重点研究了单胺氧化酶（MAO-A 和 MAO-B）和免疫标志物的变化：CD163、FOXP3、CD8 和 CX3CR1。对 OncoTherad®治疗前后的免疫反应进行了比较分析，并建立了免疫评分（IS）来评估免疫变化与临床结果的相关性。对 20 名患者的 40 个膀胱活检标本进行分组（n=20/组）：1（治疗前活检）；和 2（治疗后活检）。结果显示 MAO-A 水平稳定，但治疗后 MAO-B 免疫反应显著降低（p<0.05），提示 OncoTherad®能够靶向 MAO-B 的促肿瘤和免疫抑制功能。治疗后活检中 CD163 和 FOXP3 免疫反应明显降低（p<0.05），表明 M2 巨噬细胞和 Treg 的存在减少。与这些结果一致的是，我们观察到肿瘤组织学分级、局灶性和大小的降低，这些因素共同增强了无复发生存（RFS）和病理完全缓解（PCR）。此外，治疗后活检中 IFN-γ 免疫反应的升高与 CD8 T 细胞计数的增加和 CX3CR1 表达的升高相关，这强调了 OncoTherad®增强细胞毒性 T 细胞功能和整体抗肿瘤免疫的作用。IS 显示治疗后免疫反应改善，较高的评分与更好的 RFS 和 PCR 结果相关。这些发现验证了 OncoTherad®改变膀胱癌微环境的能力，促进有效的免疫监视和反应。
