(P 30) MYELOPEROXIDASE AS A POTENTIAL THERAPEUTIC TARGET IN SOFT TISSUE SARCOMA

Objective: Soft tissue sarcoma (STS), although a rare malignancy, is one that presents unique challenges for patients given the lack of durable systemic treatment options currently available. Prior studies have documented the extensive infiltration of tumor-associated myeloid cells (TMCs) within the sarcoma tumor microenvironment. The goal of this study is to elucidate myeloperoxidase (MPO) as a novel therapeutic target in STS as our previous work has shown that MPO is present in approximately two-thirds of patient STS resection samples.

Methods: Using a preclinical STS murine model, MCA205, we assessed the efficacy of MPO inhibition in combination with immune checkpoint inhibition (ICI). Flow cytometry was employed to characterize alterations in the immune composition of the tumor microenvironment. Histological analysis quantified MPO expression in patient sarcoma tissue samples.

Results: In the MCA205 murine model, MPO inhibition enhanced ICI response, defined by an increased survival time and delayed tumor growth in those mice treated with the MPO inhibitor in addition to ICIC compared to the control group treated only with ICI. MPO inhibition significantly increased CD8+ T cells and B cells and decreased CD11b+Ly6G+ myeloid cells within the tumor microenvironment suggesting MPO inhibition enhanced anti-tumor immune infiltration and suppressed immunosuppressive TMCs.

Conclusion: MPO serves as a potential target where its inhibition has been shown to increase ICI responses with an overall anti-tumorigenic effect in sarcoma. Given the critical need to improve durable therapeutic options in patients with STS, particularly those with advanced disease, this study serves as a preclinical foundation supporting the incorporation of MPO-specific inhibitors as an effective adjunct to immunotherapy in medical management.