posted on 2021-08-17, 02:13authored byKun Tu, Yulin Yu, Yi Wang, Ting Yang, Qian Hu, Xianya Qin, Jingyao Tu, Conglian Yang, Li Kong, Zhiping Zhang
Improving tumor immunogenicity is
critical for increasing the responsiveness
of triple-negative breast cancer (TNBC) to anti-PD-(L)1
treatment. Here, we verified that chidamide (CHI), an epigenetic modulator,
could elicit immunogenic cell death within TNBC to enhance cancer
immunogenicity and elicit an antitumor immune response. Additionally,
CHI increased the expression level of PD-L1, MHC I, and MHC II on
cancer cells, which contributed to T-cell recognition and PD-1/PD-L1
blockade therapy response. The synergistic antitumor efficacy of CHI
and PD-L1 blockade therapy was further explored through liposomes
co-delivering CHI and BMS-202 (a small-molecule PD-L1 inhibitor).
The liposomes possessed good biocompatibility, security, and controllable
drug release and endowed therapeutics drugs with favorable tumor accumulation.
Furthermore, the drug-loaded liposomes could obviously boost the antitumor
immunity of TNBC through CHI-enhanced tumor immunogenicity and BMS-202-mediated
PD-L1 blockade, thereby effectively inhibiting the growth of primary
and metastatic tumors with an inhibitory rate of metastasis of up
to 96%. In summary, this work provided a referable and optional approach
for clinical antitumor therapy based on the combination of an epigenetic
modulator and PD-1/PD-L1 blockade therapy.