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Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases

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Autor(es):
Camargo, Gabriela Cardoso de Arruda ; Oliveira, Gabriela ; Santos, Bruna Nayara Silva ; Roberto, Isadora Manzato ; Avila, Monaliza ; de Souza, Bianca Ribeiro ; Alonso, Joao Carlos Cardoso ; Duran, Nelson ; Favaro, Wagner Jose
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: MEDICAL ONCOLOGY; v. 41, n. 11, p. 16-pg., 2024-10-15.
Resumo

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 (R) (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 (R) 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 (R)'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-gamma immunoreactivities in treated biopsies correlated with increased counts of CD8(+) T cells and higher CX3CR1 expression, underscoring OncoTherad (R)'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 (R)'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response. (AU)

Processo FAPESP: 18/10052-1 - Novas Abordagens Terapêuticas para o Câncer de Bexiga Não-Músculo Invasivo (CBNMI): Uso Intravesical do Modificador de Resposta Biológica OncoTherad e Sua Associação com o Plasma Rico em Plaquetas (PRP)
Beneficiário:Wagner José Fávaro
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 22/04796-3 - Mecanismos antitumorais da nano-imunoterapia OncoTherad envolvendo a via de sinalização mediada pelo receptor toll-like 4, checkpoints imunológicos e monoamina oxidases: implicações clínicas no câncer de bexiga
Beneficiário:Gabriela Cardoso de Arruda Camargo
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 20/03419-6 - Efeitos terapêuticos e toxicológicos da imunoterapia com OncoTherad (MRB-CFI-1) em pacientes com câncer de bexiga não-músculo invasivo recidivado não responsivo à terapia com Bacillus Calmette-Guérin (BCG)
Beneficiário:Wagner José Fávaro
Modalidade de apoio: Auxílio à Pesquisa - Regular