Abstract

Conventional APCs that express MHC class II (MHCII) and co‐stimulatory molecules include dendritic cells (DCs) and macrophages. Beyond these conventional APCs, immune stimulatory cells have been more recently shown to extend to a class of atypical APCs, composed of mast cells, basophils, and eosinophils. Here, we describe a unique type of APC, Gr1−/lowCD11b−/low cells with a granularity and size characteristic of myeloid cells and with the ability to present Ag for crosspresentation. These cells constitutively express MHCII and the costimulatory molecules, CD80, CD86, and CD40. They do not express pan markers of myeloid DCs (CD11c), plasmacytoid DCs (Ly6C), or macrophages (F4/80), and their frequency is inversely correlated with myeloid‐derived suppressor cells (MDSCs) in tumor‐bearing mice. Among splenocytes, they are more abundant than DCs and macrophages, and they exhibit antitumor immune stimulatory function at a steady state without further activation, ex vivo. They are also found within the tumor bed where they retain their immune stimulatory function. Our findings suggest the use of these novel APCs in additional preclinical studies to further investigate their utility in APC‐based cancer immunotherapies.

Highlights

  • Dendritic cells (DCs) play a central role in inducing immune responses against infectious diseases and cancer

  • Using peripheral blood mononuclear cells (PBMC) of patients with early stage breast cancer, we demonstrated that conversion of myeloid-derived suppressor cell (MDSC) to CD33+CD11b−/lowHLA-DR+ APCs, in vitro, was associated with an increased frequency of CD25+ NKT cells in reprogrammed immune cells.[24]

  • LPS stimulation induced the maturation of Gr1−/lowCD11b−/low cells (Fig. 1C) by up-regulating the expression of MHC class II (MHCII) (MFI: 1851 vs. 3732, P = 0.001), CD80 (MFI: 44 vs. 87, P = 0.001), CD86 (MFI: 338 vs. 541, P = 0.008) and CD40 (MFI: 488 vs. 800, P = 0.001)

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Summary

Introduction

Dendritic cells (DCs) play a central role in inducing immune responses against infectious diseases and cancer. Their efficacy as a cell-based vaccine is limited despite continued optimization of various vaccination parameters. This is in part due to the host-derived immune suppressive cells such as myeloid-derived suppressor cells (MDSCs). The accumulation of MDSCs hinders protective immune. Received: 5 July 2017 Revised: 5 June 2018 J Leukoc Biol. 2018;104:1215–1228

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