Pheophorbide A-Mediated Photodynamic Therapy Potentiates Checkpoint Blockade Therapy of Tumor with Low PD-L1 Expression

Although the immune checkpoint blockade (ICB) has made a great success in cancer immunotherapy, the overall response rate to the ICB, such as anti-programmed death ligand 1 (PD-L1) therapy, remains only at 20-30%. One major reason is the low expression level of the immune checkpoint in a certain typ...

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Bibliographic Details
Published in:Pharmaceutics 2022-11, Vol.14 (11), p.2513
Main Authors: Tong, Qinli, Xu, Jiaojiao, Wu, Aihua, Zhang, Chen, Yang, Afeng, Zhang, Sihang, Lin, Hongzheng, Lu, Wei
Format: Article
Language:English
Subjects:
Cancer
Cancer therapies
Care and treatment
combined therapy
Health aspects
immune checkpoint blockade (ICB)
Immunotherapy
liposomes
Melanoma
Membrane proteins
Methods
pheophorbide A
Photochemotherapy
Photodynamic therapy
photodynamic therapy (PDT)
Photosensitizing compounds
programmed death ligand 1 (PD–L1)
Pyrrole
Tumors
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Summary:Although the immune checkpoint blockade (ICB) has made a great success in cancer immunotherapy, the overall response rate to the ICB, such as anti-programmed death ligand 1 (PD-L1) therapy, remains only at 20-30%. One major reason is the low expression level of the immune checkpoint in a certain type of tumor cells and its insufficient activation of the host immune system. Herein, we reported a cyclic RGD (cRGD)-modified liposomal delivery system loading the anti-PD-L1 antibody and the photosensitizer pheophorbide A (Pa), allowing a targeting of the low PD-L1 expressing 4T1 mouse breast cancer cells through the recognition of an overexpression of α β integrin on the tumor cells. The Pa-mediated photodynamic therapy (PDT) elevated the expression of PD-L1 on the tumor cells. PDT, in combination with the anti-PD-L1 therapy, promoted the activation and maturation of dendritic cells as well as the infiltration of cytotoxic T lymphocytes, resulting in the augmented antitumor immune response for the enhanced therapeutic effect. These results demonstrated the combined therapeutic effects of PDT and ICB on the tumor with low PD-L1 levels. Our study suggested that an increase in the PD-L1 expression in tumor cells by PDT would be a promising adjuvant treatment to overcome the ICB irresponsiveness.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14112513