CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

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 (C...

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Bibliographic Details
Published in:Molecular therapy. Oncolytics 2021-03, Vol.20, p.175-186
Main Authors: Pan, Yi Chun, Nishikawa, Tomoyuki, Chang, Chin Yang, Tai, Jiayu A., Kaneda, Yasufumi
Format: Article
Language:English
Subjects:
anti-PD-1
breast cancer
HVJ-E
metastasis
N1-type neutrophils
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Summary: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. [Display omitted] 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.
ISSN:2372-7705
2372-7705
DOI:10.1016/j.omto.2020.12.011