摘要
The low response rates and the following adaptive resistance have limited the therapeutic outcomes of immune checkpoint blockade(ICB)therapy.Herein,we report a local mild photothermal-chemotherapy treatment to potentiate ICB therapy for overcoming both primary and adaptive resistance,achieving a therapeutic benefit for“cold”tumors at final.We load mitoxantrone(MTO)and gambogic acid(GA)into methoxy poly(ethylene glycol)-g-poly(L-glutamic acid)(PLG-g-mPEG)nanoparticles to synergistically induce tumor immunogenic cell death and generate in situ vaccine to prime the antitumor immunity.Furthermore,local mild photothermal therapy is combined under laser irradiation to increase the tumor-infiltrating lymphocytes infiltration and reverse the immunosuppressive environments,thus amplifying the antitumor immunity.The synergetic strategy reprograms the immunosuppressive tumors toward immunogenic tumor phenotype to improve the efficacy of anti-programmed death-1/programmed death ligand 1(anti-PD)therapy in advanced 4T1 tumors,with further prevention of tumor relapse for overcoming the adaptive resistance to anti-PD therapy through downregulation of alternative immune checkpoints.Our findings demonstrate our proposed mild photothermal-chemotherapy is a potent and alternative regimen to enhance the ICB therapy for“cold”tumors in the clinic.
基金
the Jilin province science and technology development program(No.YDZJ202201ZYTS329)
the National Natural Science Foundation of China(No.52373161).
