Repolarizing immune-suppressing M2 macrophage to pro-inflammatory M1 phenotype via irreversible electroporation (IRE) reduced local tumor growth and metastases and improved overall survival in a mouse model of bladder cancer.
The findings of Featured Abstract “Adjuvant Macrophage Repolarization to M1 Phenotype Augments Post-Ablation Local Tumor Control and Improves Overall Survival in a Murine Model of Bladder Tumors” will be presented during Sunday’s Scientific Session 1, Ablation 1 in Room 221AB of the Phoenix Convention Center.
In this study, IRE was tested both on its own and in combination with supramolecular nanotherapeutic (SNT) for M1 repolarization. The treatment was evaluated with both B6 and NOD-SCID mice with bladder cancer to understand the relative role of innate and adaptive immunity.
Mice were sacrificed at several time points for flow cytometry following IRE or were kept under observation in a survival study. Flow cytometry for macrophage markers and T cell markers from tumor samples was performed. Tumor samples underwent immunohistochemistry for cell death, macrophages or T cell markers. Local tumor volume and overall survival were evaluated and compared between cohorts and mouse strains to understand cross-interactions with adaptive immunity.
The results showed that IRE stimulated robust macrophage infiltration that uniformly exhibited an immunosuppressive M2 phenotype at days three and five. SNT effectively repolarized macrophages at the site of ablation to M1 phenotype. Adjuvant SNT did not alter CD4+ and CD8+ cells but greatly reduced FoxP3+ population in vivo.
The combination therapy showed a greater reduction in local tumor growth and lung metastases and a higher overall survival rate.
“Our study indicates that immunomodulation after interventional oncology can be effective,” said presenting author Yasushi Kimura, MD, PhD, assistant professor in the radiology department at Osaka University Graduate School of Medicine in Japan. This work was carried out in the UMass Amherst lab of Dr. Kimura’s postdoctoral mentor, Govind Srimathveeravalli, PhD.
“We have been aware of macrophage activity at the site of ablation for several decades. Here we show that such cells can be recruited for combination immunotherapy strategies, creating new avenues of clinical and research investigation in interventional oncology,” Dr. Kimura said. “This study is one of combination therapies of immunotherapy and interventional oncology. We should focus on this kind of study in the future.”
