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

Menée in vitro et à l'aide de modèles murins de lymphome, de cancer du côlon ou de cancer du poumon à petites cellules, cette étude démontre que le blocage du CD47 augmente les effets antitumoraux locaux de la radiothérapie et stimule les effets abscopaux via la migration de macrophages sur les sites non irradiés

Résumé en anglais

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.