Decreased serum levels of IL-4 correlate with the efficacy of the PAI-1 inhibitor TM5614 in patients with malignant melanoma refractory to anti-PD-1 antibodies: post hoc study of TM5614-MM trial

We previously reported that the combination of the PAI-1 inhibitor TM5614 and nivolumab resulted in a 25.9% response rate in patients with anti-PD-1 antibody failure, . We therefore comprehensively evaluated serum levels of chemokines and cytokines from patients enrolled in the protocol per set cohort of the TM5614-MM clinical trial (jRCT2021210029). Our present study revealed significant reductions in IL-4, IL-16, and CXCL2 in the response group treated with TM5614.Our findings suggest that the induction of an anti-tumor response in our previous clinical trial is due to the activation of TAMs through the blockade of M2 polarization and the reduction of mo-MDSCs in the tumor-bearing host.