title: UVB-irradiated apoptotic cells induce accelerated growth of co-implanted viable tumor cells in immune competent mice.
abstract: The presence of a solid tumor is the result of a complex balance between rejection, tolerance and regeneration in which the interactions of tumor cells with cells of the host immune system contribute strongly to the final outcome. Here we report on a model where lethally UVB-irradiated cells cause accelerated growth of viable tumor cells in vitro and in allogeneic immune competent mice. UVB-irradiated tumor cells alone did not form tumors and failed to induce tolerance for a second challenge with the same allogeneic tumor. Our data show an important role for dying cells in promoting accelerated tumor cell growth of a small number of viable tumor cells in a large inoculum of UVB-irradiated tumor cells. This occurs when viable and dying/dead tumor cells are in close proximity, suggesting that mobile factors contribute to growth promotion. The anti-inflammatory and growth promoting properties of apoptotic cells are based on several independent effects. UVB-irradiated apoptotic cells directly release a growth promoting activity and clearance by macrophages of apoptotic cells is accompanied by the secretion of IL10, TGFß, and PGE2. Growth promotion is even observed with dying heterologous cells implying a conserved mechanism. Future experiments should focus on the effects of dying tumor cells generated in vivo on the outgrowth of surviving tumor cells which is prone to have implications for cancer therapy.
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Chaurio
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.forename: Christine
authors.initials: C
authors.lastname: Schorn
authors.forename: Christian
authors.initials: C
authors.lastname: Maueröder
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Bilyy
authors.forename: Udo
authors.initials: U
authors.lastname: Gaipl
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
authors.forename: Benjamin
authors.initials: B
authors.lastname: Frey
authors.forename: Luis E
authors.initials: LE
authors.lastname: Munoz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004195:Disease Models, Animal; D007121:Immunocompetence / Q000276:immunology* / Q000528:radiation effects; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation*; D014466:Ultraviolet Rays