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.
Medical oncology (Northwood, London, England). 2024 Oct 15*** epublish ***
Gabriela Cardoso de Arruda Camargo, Gabriela Oliveira, Bruna Nayara Silva Santos, Isadora Manzato Roberto, Monaliza Ávila, Bianca Ribeiro de Souza, João Carlos Cardoso Alonso, Nelson Durán, Wagner José Fávaro
Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), CP-6109, Campinas, São Paulo, 13083-865, Brazil. ., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), CP-6109, Campinas, São Paulo, 13083-865, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), CP-6109, Campinas, São Paulo, 13083-865, Brazil. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39404781