Plasmacytoid dendritic cells play a key role in tumor progression in lipopolysaccharide-stimulated lung tumor-bearing mice.
The antitumor activity of LPS was first described by Dr. William Coley. However, its role in lung cancer remains unclear. The aim of our study was to elucidate the dose-dependent effects of LPS (0.1-10 μg/mouse) in a mouse model of B16-F10-induced metastatic lung cancer. Lung tumor growth increased at 3 and 7 d after the administration of low-dose LPS (0.1 μg/mouse) compared with control mice. This was associated with an influx of plasmacytoid dendritic cells (pDCs), regulatory T cells, myeloid-derived suppressor cells, and CD8(+) regulatory T cells. In contrast, high-dose LPS (10 μg/mouse) reduced lung tumor burden and was associated with a greater influx of pDCs, as well as a stronger Th1 and Th17 polarization. Depletion of pDCs during low-dose LPS administration resulted in a decreased lung tumor burden. Depletion of pDCs during high-dose LPS treatment resulted in an increased tumor burden. The dichotomy in LPS effects was due to the phenotype of pDCs, which were immunosuppressive after the low-dose LPS, and Th1- and T cytotoxic-polarizing cells after the high-dose LPS. Adoptive transfer of T cells into nude mice demonstrated that CD8(+) T cells were responsible for pDC recruitment following low-dose LPS administration, whereas CD4(+) T cells were required for pDC influx after the high-dose LPS. In conclusion, our data suggest differential effects of low-dose versus high-dose LPS on pDC phenotype and tumor progression or regression in the lungs of mice.
Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano 84084, Italy. rsorrentino@unisa.it
Alessia
A
Rega
Michela
M
Terlizzi
Antonio
A
Luciano
Giovanni
G
Forte
Timothy R
TR
Crother
Claudio
C
Arra
Moshe
M
Arditi
Aldo
A
Pinto
Rosalinda
R
Sorrentino
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D008070:Lipopolysaccharides