Open AccessRadiation combined with macrophage depletion promotes adaptive immunity and potentiates checkpoint blockade
Author(s) -
Jones Keaton I,
Tiersma Jiske,
Yuzhalin Arseniy E,
GordonWeeks Alex N,
Buzzelli Jon,
Im Jae Hong,
Muschel Ruth J
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809342
Subject(s) - macrophage , cancer research , immune system , cd8 , immunology , immunity , immunosuppression , acquired immune system , biology , antigen , priming (agriculture) , in vitro , biochemistry , botany , germination
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 ( MC 38) 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 ( TAM s) 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 CD 8 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.