Blockade

CD47

Biology

Receptor

Lung cancer

Cancer research

Biochemistry

Bystander effect

Radiation therapy

Immunology

Radiosensitivity

Immune system

In vitro

Macrophage

Abscopal effect

Internal medicine

Oncology

Medicine

Chemistry

Immunotherapy

Phagocytosis

Cancer

Nature Cancer

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.

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