A Combination of GM-CSF and Released Factors from Gamma-Irradiated Tumor Cells Enhances the Differentiation of Macrophages from Bone Marrow Cells and Their Antigen-Presenting Function and Polarization to Type 1.

Lichao Chen,Hiroshi Igaki,Ying Tong,Satoshi Nakamura,Takae Onodera,Mitsuko Masutani,Shoji Imamichi,Yuka Sasaki,Jun Itami

doi:10.3390/medicines8070035

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes dendritic cell differentiation from precursors, and consequently, enhances the antigen presentation process and adaptive immune responses. With such functions, GM-CSF has been used as immunotherapy in combination with radiotherapy for cancer treatment to augment the survival and activity of immune cells. However, an immune-suppressive tumor microenvironment may cause anergy of T cells. It has also been reported that GM-CSF contributes to the development of myeloid-derived suppressor cells from the precursors. In this study, to analyze the combined effect of GM-CSF and released factors from cancer cells after gamma-ray irradiation on bone marrow cell differentiation and dynamics, we established an in vitro culture system using mouse bone marrow cells, GM-CSF, and conditioned medium from gamma ray irradiated mouse melanoma B16 cells at 24 Gy. We analyzed the gene expression changes of the bone marrow-derived cells on day 6. The results showed that GM-CSF dose-dependently enhanced the differentiation of macrophages from bone marrow cells, their antigen-presenting function and polarization to type I. The results implied the induced macrophages from the bone marrow may potentially contribute to tumor immune responses in a systemic manner when GM-CSF is boosted during photon-beam radiation therapy.

Highlights

Introduction iationsGranulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the cell proliferation, differentiation, and survival of leukocytes [1,2,3]
Taking into account the fact that GM-CSF is able to activate and process the presentation of tumor-associated antigens by dendritic cell (DC)s, GM-CSF was studied in clinical trials by overexpressing in tumor cells, but significant therapeutic outcomes were not obtained [4,5]
In the presence of GM-CSF, adherent cells loosely/non-adherent cell were survived on day 6

Summary

Introduction

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the cell proliferation, differentiation, and survival of leukocytes [1,2,3]. Taking into account the fact that GM-CSF is able to activate and process the presentation of tumor-associated antigens by dendritic cell (DC)s, GM-CSF was studied in clinical trials by overexpressing in tumor cells, but significant therapeutic outcomes were not obtained [4,5]. GM-CSF has been used during radiotherapy to increase immune cell activation and survival. Around 30% of patients showed shrinkage of tumors at non-irradiated sites as an abscopal response, the mechanism is not clearly understood [6]. The hypothesis for abscopal response induction mediated, at least partly by GM-CSF, is that GM-CSF systemically may promote the maturation of DCs. the presentation of tumor antigen to naive T cells may be improved.

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Conclusion