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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.
Afiliação
  • Nishiga Y; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Drainas AP; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Baron M; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Bhattacharya D; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Barkal AA; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Ahrari Y; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Mancusi R; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Ross JB; Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Takahashi N; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Thomas A; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Diehn M; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA.
  • Weissman IL; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Graves EE; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Sage J; Department of Pediatrics, Stanford University, Stanford, CA, USA.
Nat Cancer ; 3(11): 1351-1366, 2022 11.
Article em En | MEDLINE | ID: mdl-36411318
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Pequenas Células do Pulmão / Neoplasias Pulmonares Limite: Animals Idioma: En Revista: Nat Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Pequenas Células do Pulmão / Neoplasias Pulmonares Limite: Animals Idioma: En Revista: Nat Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos