Decreased interleukin 4 serum levels correlate with plasminogen activator inhibitor-1 inhibitor TM5614 efficacy in patients with malignant melanoma refractory to anti-programmed cell death protein-1 antibodies: post hoc study of the TM5614-MM trial

We previously reported that a 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 the serum levels of chemokines and cytokines in 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 antitumour response in our previous clinical trial was due to the activation of tumour-associated macrophages through the blockade of M2 polarization and the reduction of monocytic myeloid-derived suppressor cells in the tumour-bearing host.