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

Med Oncol. 2024 Oct 15;41(11):287. doi: 10.1007/s12032-024-02533-z.

Abstract

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.

Keywords: Bladder cancer; Immune biomarkers; Immunotherapy; Monoamine oxidase; OncoTherad® (MRB-CFI-1); Tumor microenvironment.

Publication types

  • Editorial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Immunotherapy* / methods
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Male
  • Middle Aged
  • Monoamine Oxidase* / metabolism
  • Non-Muscle Invasive Bladder Neoplasms
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / immunology
  • Tumor-Associated Macrophages* / drug effects
  • Tumor-Associated Macrophages* / immunology
  • Tumor-Associated Macrophages* / metabolism
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / immunology
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Monoamine Oxidase