447 Development of the combination therapy of anti-PD1 antibody with PAI-1 inhibitors in advanced melanoma patients

Plasminogen activating inhibitor-1 (PAI-1) is associated with poor clinical outcomes in cancer patients, and elevated levels of PAI-1 both tissue serum are correlated response to therapy various cancers, including skin cancer. reported as a key regulator PD-L1 expression on melanoma cells through endocytosis, leading abrogating the efficacy anti-PD1 antibodies (Abs). These findings suggested that might predict Abs. From above findings, at first, we evaluated production patients who treated Abs, then, investigated immunomodulatory effects tumor-associated macrophages vitro. Immunohistochemical staining showed was significantly decreased Abs responded compared non-responded patients. Moreover, baseline were Notably, chemokines from monocyte-derived M2 vitro, suggesting decrease tumor-infiltrating lymphocytes hamper anti-tumor To further confirm this hypothesis, inhibitors (TM5614) combination using B16F10 mouse model. The co-administration TM5614 augmented therapeutic effect treatment melanoma. results suggest enhance nivolumab advanced melanoma, phase II study investigating safety unresectable malignant now ongoing (jRCT2021210029).