Platinum(IV) complexes as inhibitors of CD47-SIRPα axis for chemoimmunotherapy of cancer.
Eur J Med Chem
; 229: 114047, 2022 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-34915428
ABSTRACT
Phagocytosis of cancer cells by antigen presenting cells (APCs) is critical to activate the host's immune responses. However, the targeting ability of APCs to cancer cells is limited by the upregulation of transmembrane protein CD47 on the cancer cell surface. Blocking CD47 can affect the macrophage-mediated phagocytosis. Two platinum-based immunomodulators MUP and DMUP were synthesized to enhance the phagocytic activity of macrophages by blocking the CD47-SIRPα axis. These PtIV complexes not only showed high antiproliferative activity against a panel of human cancer cell lines, but also cooperated with human peripheral blood mononuclear cells (PBMCs) to suppress cancer cells. They acted as immune checkpoint inhibitors to modulate the immune responses of both cancer and immune cells. In particular, DMUP decreased the expression of CD47 in tumor tissues and promoted the polarization of macrophages from M2 to M1 phenotype in a mouse model of non-small cell lung cancer, thereby enhancing the anticancer effect. By interfering with DNA synthesis and stimulating immune system, DMUP takes the advantage of chemotherapy and immunotherapy to inhibit cancer cells. The dual efficacy of DMUP makes it a potential chemoimmunotherapeutic agent in cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Receptores Imunológicos
/
Antígeno CD47
/
Complexos de Coordenação
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2022
Tipo de documento:
Article