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Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect
Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the ‘don’t-eat-me’ cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enh...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701141/ https://www.ncbi.nlm.nih.gov/pubmed/36411318 http://dx.doi.org/10.1038/s43018-022-00456-0 |
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author | Nishiga, Yoko Drainas, Alexandros P. Baron, Maya Bhattacharya, Debadrita Barkal, Amira A. Ahrari, Yasaman Mancusi, Rebecca Ross, Jason B. Takahashi, Nobuyuki Thomas, Anish Diehn, Maximilian Weissman, Irving L. Graves, Edward E. Sage, Julien |
author_facet | Nishiga, Yoko Drainas, Alexandros P. Baron, Maya Bhattacharya, Debadrita Barkal, Amira A. Ahrari, Yasaman Mancusi, Rebecca Ross, Jason B. Takahashi, Nobuyuki Thomas, Anish Diehn, Maximilian Weissman, Irving L. Graves, Edward E. Sage, Julien |
author_sort | Nishiga, Yoko |
collection | PubMed |
description | Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the ‘don’t-eat-me’ cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enhances the local antitumor effects of radiotherapy in preclinical models of SCLC. Notably, CD47 blockade also stimulates off-target ‘abscopal’ effects inhibiting non-irradiated SCLC tumors in mice receiving radiation. These abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by radiation and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal antitumor effects were observed in other cancer models treated with radiation and CD47 blockade. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in patients with cancer who suffer from metastatic disease. |
format | Online Article Text |
id | pubmed-9701141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-97011412022-11-28 Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect Nishiga, Yoko Drainas, Alexandros P. Baron, Maya Bhattacharya, Debadrita Barkal, Amira A. Ahrari, Yasaman Mancusi, Rebecca Ross, Jason B. Takahashi, Nobuyuki Thomas, Anish Diehn, Maximilian Weissman, Irving L. Graves, Edward E. Sage, Julien Nat Cancer Article Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the ‘don’t-eat-me’ cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enhances the local antitumor effects of radiotherapy in preclinical models of SCLC. Notably, CD47 blockade also stimulates off-target ‘abscopal’ effects inhibiting non-irradiated SCLC tumors in mice receiving radiation. These abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by radiation and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal antitumor effects were observed in other cancer models treated with radiation and CD47 blockade. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in patients with cancer who suffer from metastatic disease. Nature Publishing Group US 2022-11-21 2022 /pmc/articles/PMC9701141/ /pubmed/36411318 http://dx.doi.org/10.1038/s43018-022-00456-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nishiga, Yoko Drainas, Alexandros P. Baron, Maya Bhattacharya, Debadrita Barkal, Amira A. Ahrari, Yasaman Mancusi, Rebecca Ross, Jason B. Takahashi, Nobuyuki Thomas, Anish Diehn, Maximilian Weissman, Irving L. Graves, Edward E. Sage, Julien Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title | Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title_full | Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title_fullStr | Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title_full_unstemmed | Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title_short | Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect |
title_sort | radiotherapy in combination with cd47 blockade elicits a macrophage-mediated abscopal effect |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701141/ https://www.ncbi.nlm.nih.gov/pubmed/36411318 http://dx.doi.org/10.1038/s43018-022-00456-0 |
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