Nishiga et al. demonstrated that irradiation and CD47 blockade significantly inhibited tumor growth and led to abscopal effects in non-irradiated tumors in a macrophage-dependent and T cell-independent manner in multiple preclinical models. Irradiation of SCLC cells induced secretion of CSF1 and other inflammatory cytokines at the irradiated tumor site, and enhanced the migratory capacity of macrophages, leading to abscopal responses. CD47 blockade is required at both the irradiated and non-irradiated tumors, but not required systemically. In a colon cancer model, PD-1 blockade enhanced the abscopal effects of radiation therapy and CD47 blockade.
Contributed by Shishir Pant
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.
Author Info: (1) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford Uni
Author Info: (1) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford University, Stanford, CA, USA. (2) Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford University, Stanford, CA, USA. (3) Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford University, Stanford, CA, USA. (4) Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford University, Stanford, CA, USA. (5) Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA. Department of Pathology, Stanford University, Stanford, CA, USA. (6) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. (7) Department of Pediatrics, Stanford University, Stanford, CA, USA. Department of Genetics, Stanford University, Stanford, CA, USA. (8) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. (9) Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. (10) Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. (11) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. (12) Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA. Department of Pathology, Stanford University, Stanford, CA, USA. (13) Department of Radiation Oncology, Stanford University, Stanford, CA, USA. egraves@stanford.edu. (14) Department of Pediatrics, Stanford University, Stanford, CA, USA. julsage@stanford.edu. Department of Genetics, Stanford University, Stanford, CA, USA. julsage@stanford.edu.
