Antitumor efficacy of radiation plus immunotherapy depends upon dendritic cell activation of effector CD8+ T cells.
Authors
Dovedi, SLipowska-Bhalla, G
Beers, S
Cheadle, Eleanor J
Mu, L
Glennie, M
Illidge, Timothy M
Honeychurch, Jamie
Affiliation
Targeted Therapy Group, School of Cancer and Enabling Sciences, University of ManchesterIssue Date
2016-05-30
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Show full item recordAbstract
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); 1-10. ©2016 AACR.Citation
Antitumor efficacy of radiation plus immunotherapy depends upon dendritic cell activation of effector CD8+ T cells. 2016: Cancer Immunol ResJournal
Cancer Immunology ResearchDOI
10.1158/2326-6066.CIR-15-0253PubMed ID
27241845Type
ArticleLanguage
enISSN
2326-6074ae974a485f413a2113503eed53cd6c53
10.1158/2326-6066.CIR-15-0253
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