Dados do Trabalho

Título

Enhancing Immunological Responses in Non-Muscle Invasive Bladder Cancer: Effects of OncoTherad® (MRB-CFI-1) Immunotherapy on the Tumor Microenvironment, Focusing on Tumor-Associated Macrophages, Tumor-Infiltrating Lymphocytes and Monoamine Oxidases

Resumo

Non-muscle invasive bladder cancer (NMIBC) presents significant management challenges due to its high recurrence rate and a complex tumor microenvironment (TME) that often suppresses effective immune responses. This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, specifically focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers including CD163, FOXP3, CD8, and CX3CR1. We conducted a comparative analysis of immunoreactivities in bladder biopsies taken before and after OncoTherad® (MRB-CFI-1) treatment and established an immune score (IS) to evaluate the correlation between immunological changes and clinical outcomes. Forty formalin-fixed, paraffin-embedded bladder tissue samples from 20 patients, aged 44 to 83 years (mean 63.5 years), who were diagnosed with BCG-unresponsive NMIBC e, posteriormente tratados com OncoTherad® (MRB-CFI-1). Bladder biopsies of each patient were divided into 2 groups (n= 20 samples per group): Group 1 (initial biopsy, before OncoTherad treatment); and Group 2 (bladder biopsy after OncoTherad treatment). 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. Also, 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. This shift points to OncoTherad®'s role in reducing immunosuppression within the bladder TME, thereby potentially improving immune response to the tumor. Corresponding with these immunological changes, 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. Implementation of an IS revealed significant 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.

Palavras Chave

Bladder cancer; tumor microenvironment; immunotherapy