Radiation combined with macrophage depletion promotes adaptive immunity and potentiates checkpoint blockade

EMBO Molecular Medicine

Keaton I Jones¹  Jon Buzzelli¹  Arseniy E Yuzhalin¹  Jae Hong Im¹  Ruth J Muschel¹  Jiske Tiersma¹  Alex N Gordon‐Weeks² 

[1] Department of Oncology CRUK/MRC Oxford Institute for Radiation Oncology Churchill Hospital University of Oxford Oxford UK;Nuffield Department of Surgical Sciences John Radcliffe Hospital University of Oxford Oxford UK;

关键词: immunosuppression;    immunotherapy;    macrophage;    radiation;   

DOI  :  10.15252/emmm.201809342

来源: DOAJ

【 摘 要 】

Abstract Emerging evidence suggests a role for radiation in eliciting anti‐tumour immunity. We aimed to investigate the role of macrophages in modulating the immune response to radiation. Irradiation to murine tumours generated from colorectal (MC38) and pancreatic (KPC) cell lines induced colony‐stimulating factor 1 (CSF‐1). Coincident with the elevation in CSF‐1, macrophages increased in tumours, peaking 5 days following irradiation. These tumour‐associated macrophages (TAMs) were skewed towards an immunosuppressive phenotype. Macrophage depletion via anti‐CSF (aCSF) reduced macrophage numbers, yet only achieved tumour growth delay when combined with radiation. The tumour growth delay from aCSF after radiation was abrogated by depletion of CD8 T cells. There was enhanced recognition of tumour cell antigens by T cells isolated from irradiated tumours, consistent with increased antigen priming. The addition of anti‐PD‐L1 (aPD‐L1) resulted in improved tumour suppression and even regression in some tumours. In summary, we show that adaptive immunity induced by radiation is limited by the recruitment of highly immunosuppressive macrophages. Macrophage depletion partly reduced immunosuppression, but additional treatment with anti‐PD‐L1 was required to achieve tumour regression.

【 授权许可】

Unknown