Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect

Yoko Nishiga; Alexandros P Drainas; Maya Baron; Debadrita Bhattacharya; Amira A Barkal; Yasaman Ahrari; Rebecca Mancusi; Jason B Ross; Nobuyuki Takahashi; Anish Thomas; Maximilian Diehn; Irving L Weissman; Edward E Graves; Julien Sage

doi:10.1038/s43018-022-00456-0

Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect

Nat Cancer. 2022 Nov;3(11):1351-1366. doi: 10.1038/s43018-022-00456-0. Epub 2022 Nov 21.

Authors

Yoko Nishiga^{1

2

3}, Alexandros P Drainas^{2

3}, Maya Baron^{2

3}, Debadrita Bhattacharya^{2

3}, Amira A Barkal^{4

5

6}, Yasaman Ahrari¹, Rebecca Mancusi^{2

3}, Jason B Ross¹, Nobuyuki Takahashi^{7

8}, Anish Thomas⁷, Maximilian Diehn¹, Irving L Weissman^{4

5

6}, Edward E Graves⁹, Julien Sage^{10

11}

Affiliations

¹ Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
² Department of Pediatrics, Stanford University, Stanford, CA, USA.
³ Department of Genetics, Stanford University, Stanford, CA, USA.
⁴ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
⁵ Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA.
⁶ Department of Pathology, Stanford University, Stanford, CA, USA.
⁷ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁸ Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
⁹ Department of Radiation Oncology, Stanford University, Stanford, CA, USA. egraves@stanford.edu.
¹⁰ Department of Pediatrics, Stanford University, Stanford, CA, USA. julsage@stanford.edu.
¹¹ Department of Genetics, Stanford University, Stanford, CA, USA. julsage@stanford.edu.

Abstract

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD47 Antigen
Lung Neoplasms* / drug therapy
Macrophages
Mice
Phagocytosis
Small Cell Lung Carcinoma* / drug therapy

Substances

CD47 Antigen

Abstract

Publication types

MeSH terms

Substances

Grants and funding