Abstract
Abstract Treatment of pancreatic cancer is faced with great difficulties and challenges due to high lethality and metastasis. Synergism of targeted therapy and immunotherapy has been considered as ideal strategy to both eliminate primary tumors and control metastases. For the treatment of advanced pancreatic cancer, we demonstrated a local photothermal therapy (PTT) following administration of monoclonal antibody of programmed death ligand 1 (αPD-L1). Fe2P nanorods were employed as a Fenton agent and photothermal agent, which modified with DSPE-PEG2000-Mal for improved biocompatibility and Mal mediated-antigen presentation. Under a low dose laser irradiation at 980 nm, Fe2P-PEG-Mal nanorods (NRs) mediated PTT could induce immunogenic tumor cell death that can cause dendritic cells (DCs) infiltration and maturation. In a bilateral pancreatic tumor model, the local treatment of NRs-PTT on primary tumor could cause the increased infiltration of cytotoxic T lymphocytes (CTLs) and decreased residential of M2 macrophages in untreated distal tumors. Furthermore, subsequently intervened αPD-L1 could enhance cell death triggered by CTLs in distal tumors through reversing immunosuppression. An orthotopic pancreatic tumor model was used to further confirm the therapeutic outcome. Finally, the combination of NRs based PTT and αPD-L1 based immunotherapy was able to significantly eliminate orthotopic pancreatic tumors and reduce mesentery metastases. Thus, the strategy may provide a more effective treatment for pancreatic cancer.
Highlights
Pancreatic cancer is one of the most lethal malignancies with high fatality rate, poor curative effect, and unsatisfactory prognosis [1]
For the treatment of advanced pancreatic cancer, we demonstrated a local photothermal therapy (PTT) following administration of monoclonal antibody of programmed death ligand 1
The efficacy of chemotherapy and radiotherapy could be restricted by dense tumor stroma and uneven dose distribution in pancreatic tumor, respectively [6, 7]
Summary
Pancreatic cancer is one of the most lethal malignancies with high fatality rate, poor curative effect, and unsatisfactory prognosis [1]. The efficacy of chemotherapy and radiotherapy could be restricted by dense tumor stroma and uneven dose distribution in pancreatic tumor, respectively [6, 7] These two traditional therapies have limited efficacy on metastases [8, 9]. Ipilimumab, a CTLA-4 inhibitor, combined with PTT exhibited the remarkable therapeutic outcomes to completely clear subcutaneous and distal lung metastases on a stage IV melanoma patient [24]. Inspired by such properties, combination between PTT and immunotherapy will be a promising therapy modality for pancreatic cancer to cause ablation of primary tumor, and activation of immunity to control tumor metastasis. Antitumor activity and immune response were studied in vitro and in vivo
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