CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
| Autor: | Jiayu A. Tai, Yasufumi Kaneda, Tomoyuki Nishikawa, Yi Chun Pan, Chin Yang Chang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment HVJ-E N1-type neutrophils lcsh:RC254-282 Metastasis 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer Cancer immunotherapy medicine metastasis Cytotoxic T cell Pharmacology (medical) Tumor microenvironment biology Chemistry Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research anti-PD-1 Molecular Medicine Original Article Antibody |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 20, Iss, Pp 175-186 (2021) Molecular Therapy Oncolytics |
| ISSN: | 2372-7705 |
| Popis: | Breast cancer has a high risk of metastasis; however, no effective treatment has been established. We developed a novel immunotherapy for breast cancer to enhance cytotoxic T lymphocytes against cancer cells using N1-type neutrophils with anti-tumor properties. For this purpose, we combined CXCL2 (CXC chemokine ligand 2) plasmid DNA with inactivated Sendai virus (hemagglutinating virus of Japan)-envelope (HVJ-E). The combination of CXCL2 DNA and HVJ-E (C/H) suppressed the growth of murine breast cancers in orthotopic syngeneic models by enhancing cytotoxic T lymphocytes and inhibited lung metastasis of breast cancer from primary lesions. N1-type neutrophils (CD11b+ Ly6G+ FAS+) increased in the tumor microenvironment with C/H treatment, and tumor suppression and cytotoxic T lymphocyte activation from C/H was blocked after administrating anti-neutrophil antibodies, which indicates the role of N1-type neutrophils in cancer immunotherapy. We also demonstrated that the anti-tumor activities of C/H treatment were enhanced by the administration of anti-PD-1 antibodies through neutrophil-mediated cytotoxic T lymphocyte activation. Thus, the triple combination of C/H and anti-PD-1 antibody C/H treatment may provide an improvement in cancer immunotherapy. Graphical Abstract The combination of CXCL2 plasmid DNA and HVJ-E treatment polarized neutrophils to N1 neutrophils, which activated CTL to suppress both primary and metastatic murine breast cancer legions. The anti-tumor effect of the combination therapy using CXCL2 plasmid DNA and HVJ-E was enhanced by anti-PD-1 antibody treatment. |
| Databáze: | OpenAIRE |
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