Platinum(IV) Complexes Trigger Death Receptors and Natural Killer Cells to Suppress Breast Cancer

Chemoimmunotherapy is an alternative treatment against
cancers.
Platinum(IV) complexes FMP and DFMP, coupling formononetin derivative
as axial ligand(s), were designed to suppress triple-negative breast
cancer (TNBC) by activating death receptors (DRs) and natural killer
(NK) cells. These complexes show great potential to overcome the resistance
of TNBC to chemotherapy by inducing both intrinsic and extrinsic apoptosis
in cancer cells. Particularly, FMP with one axial formononetin derivative
not only induced the caspase-3-dependent intrinsic apoptosis but also
upregulated the expression of DRs and caspase-8, triggered the extrinsic
apoptosis, and enhanced the cytotoxic ability of NK92 cells. Moreover,
FMP increased the release of granzyme B, restrained the proliferation
and differentiation of myeloid-derived suppressor cells, and the secretion
of IL-10, thus inhibiting the TNBC in vitro and in vivo. The results
demonstrate that FMP overcomes the chemoresistance and immune escape
of TNBC through a new mechanism involving the synergy of chemotherapy
and immunotherapy.