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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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Autores principales: Pan, Yi Chun, Nishikawa, Tomoyuki, Chang, Chin Yang, Tai, Jiayu A., Kaneda, Yasufumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851488/
https://www.ncbi.nlm.nih.gov/pubmed/33575480
http://dx.doi.org/10.1016/j.omto.2020.12.011
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author Pan, Yi Chun
Nishikawa, Tomoyuki
Chang, Chin Yang
Tai, Jiayu A.
Kaneda, Yasufumi
author_facet Pan, Yi Chun
Nishikawa, Tomoyuki
Chang, Chin Yang
Tai, Jiayu A.
Kaneda, Yasufumi
author_sort Pan, Yi Chun
collection PubMed
description 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.
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spelling pubmed-78514882021-02-10 CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy Pan, Yi Chun Nishikawa, Tomoyuki Chang, Chin Yang Tai, Jiayu A. Kaneda, Yasufumi Mol Ther Oncolytics Original Article 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. American Society of Gene & Cell Therapy 2020-12-25 /pmc/articles/PMC7851488/ /pubmed/33575480 http://dx.doi.org/10.1016/j.omto.2020.12.011 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Pan, Yi Chun
Nishikawa, Tomoyuki
Chang, Chin Yang
Tai, Jiayu A.
Kaneda, Yasufumi
CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title_full CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title_fullStr CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title_full_unstemmed CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title_short CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy
title_sort cxcl2 combined with hvj-e suppresses tumor growth and lung metastasis in breast cancer and enhances anti-pd-1 antibody therapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851488/
https://www.ncbi.nlm.nih.gov/pubmed/33575480
http://dx.doi.org/10.1016/j.omto.2020.12.011
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