Pro-inflammatory allogeneic DCs promote activation of bystander immune cells and thereby license antigen-specific T-cell responses

Fotaki, GrammatikiUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi (author)

Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.

Jin, Chuan,1986-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)chuji162 (author)
Ramachandran, Mohanraj,1988-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)mohra272 (author)
Kerzeli, Iliana KyriakiUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)iliky579 (author)
Karlsson-Parra, AlexUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Immunicum AB, Uppsala(Swepub:uu)aka12694 (author)
Yu, Di,1985-Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)diayu422 (author)
Essand, MagnusUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)magnessa (author)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

By the author/editor: Fotaki, Grammati ...; Jin, Chuan, 1986 ...; Ramachandran, Mo ...; Kerzeli, Iliana ...; Karlsson-Parra, ...; Yu, Di, 1985-; show more...; Essand, Magnus; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.