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Cancer Immunol Res. 2016 Jul;4(7):621-630. doi: 10.1158/2326-6066.CIR-15-0253. Epub 2016 May 30.

Antitumor Efficacy of Radiation plus Immunotherapy Depends upon Dendritic Cell Activation of Effector CD8+ T Cells.

Author information

1
Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Sciences Centre, United Kingdom.
2
Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
3
The Second Affiliated Hospital, Dalian Medical University, Dalian 116027, China.
4
Christie NHS Trust, University of Manchester, Manchester Academic Health Sciences Centre, United Kingdom.
#
Contributed equally

Abstract

Tumor cells dying after cytotoxic therapy are a potential source of antigen for T-cell priming. Antigen-presenting cells (APC) can cross-present MHC I-restricted peptides after the uptake of dying cells. Depending on the nature of the surrounding environmental signals, APCs then orchestrate a spectrum of responses ranging from immune activation to inhibition. Previously, we had demonstrated that combining radiation with either agonistic monoclonal antibody (mAb) to CD40 or a systemically administered TLR7 agonist could enhance CD8 T-cell-dependent protection against syngeneic murine lymphoma models. However, it remains unknown how individual APC populations affect this antitumor immune response. Using APC depletion models, we now show that dendritic cells (DC), but not macrophages or B cells, were responsible for the generation of long-term immunologic protection following combination therapy with radiotherapy and either agonistic CD40 mAb or systemic TLR7 agonist therapy. Novel immunotherapeutic approaches that augment antigen uptake and presentation by DCs may further enhance the generation of therapeutic antitumor immune responses, leading to improved outcomes after radiotherapy. Cancer Immunol Res; 4(7); 621-30.

PMID:
27241845
PMCID:
PMC5348028
DOI:
10.1158/2326-6066.CIR-15-0253
[Indexed for MEDLINE]
Free PMC Article

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