CD11c+ MHCIIlo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma

Cancer Immunology, Immunotherapy : CII
Hakimeh Ebrahimi-NikPramod K Srivastava

Abstract

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c+ MHCIIlo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c+ MHCIIhi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.

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Citations

Apr 10, 2018·PloS One·Pouya Tavousi
Jun 21, 2019·JCI Insight·Hakimeh Ebrahimi-NikPramod K Srivastava
Oct 28, 2019·Oncoimmunology·Jenny SprootenAbhishek D Garg
Dec 16, 2020·The Journal of Clinical Investigation·Cory A BrennickPramod K Srivastava
Apr 29, 2021·Nature Reviews. Cancer·Mansi SaxenaNina Bhardwaj
Aug 8, 2021·International Journal of Molecular Sciences·Akshita ChauhanAbdelwahab Omri

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
transgenic
scraping
Flow cytometry
RNA-Seq
light microscopy

Software Mentioned

MACS
HISAT2
IPA
IsoDE2
GraphPad Prism
Morpheus
IsoEM2
ingenuity pathway analysis ( IPA )

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