CD11c MHCII 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

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2018 Jul 22

PMID 30030558

Citations 12

Authors

Hakimeh Ebrahimi-Nik

William L Corwin

Tatiana Shcheglova

Alok Das Mohapatra

Ion I Mandoiu

Pramod K Srivastava

Affiliations

Soon will be listed here.

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 MHCII 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 MHCII 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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