Effects of IL-1 molecules on growth patterns of 3-MCA-induced cell lines: an interplay between immunogenicity and invasive potential.
The balance between inflammation and immunity is cardinal for the outcome of the malignant process. Local attenuated inflammatory responses mediated by innate cells may provide accessory signals for the development of acquired immunity against malignant cells. In contrast, excessive inflammatory responses accompany tumorigenesis and tumor invasiveness, by the induction of immunosuppression. In the present study, we have assessed the role of tumor cell-derived IL-1 in determining the invasive versus immunostimulatory potential of tumor cells. For this purpose, we have used 3-MCA-induced fibrosarcoma cell lines from IL-1 knockout (KO) versus control mice. Cell lines with no IL-1 failed to establish tumors in intact mice, while lines obtained from control mice were invasive and induced a potent angiogenic response. In contrast, cell lines from IL-1KO mice were more immunogenic. SDF-1 and IL-6, each induced by IL-1, were the two major cytokines whose levels differed in cell lines with or without IL-1. We could not detect differences in cell surface markers related to immunogenicity, such as MHC Class I, co-stimulatory, or adhesion molecules between both types of cells. However, more T-cells were observed at the inoculation site of tumor cells devoid of IL-1 and more pronounced parameters related to anti-tumor immunity were observed in the spleen (IL-12 and IFNgamma) of these mice, compared to mice bearing tumors derived from control mice, where host-derived IL-1 is present. In addition, injection of tumor cells devoid of IL-1, which failed to grow in mice, induced an anti-tumor cell immune memory, while in mice injected with tumor cells from control mice; no immune memory could be detected. From the results, it seems that IL-1 is a crucial factor in determining the balance between immunity and inflammation in tumor-bearing mice. This suggests that manipulation of IL-1 could be useful in anti-tumor therapy, by reducing invasiveness and promoting immunity against the malignant cells.
Voronov
Elena
E
The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. elena@bgu.ac.il
Reich
Eli
E
Dotan
Shahar
S
Dransh
Pavel
P
Cohen
Idan
I
Huszar
Monica
M
Fogel
Mina
M
Kleinman
Hynda K
HK
White
Rosalyn M
RM
Apte
Ron N
RN
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D045744:Cell Line, Tumor; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007375:Interleukin-1 / Q000172:deficiency / Q000276:immunology*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016207:Cytokines; D007375:Interleukin-1; D008748:Methylcholanthrene