Granulocytes as effective anticancer agent in experimental solid tumor models.
The aim of the study was to elucidate the effects of murine granulocytes on the growth of solid murine tumors when administrated in the vicinity of W256 carcinoma growing in Sprague Dawley rats, and in the vicinity of Ehrlich ascites tumor (EAT) growing in BALBc mice. The administration of granulocytes significantly improved the survival of W256-bearing rats, and increased the tumor regression incidence from 17% up to 75%. Rats with regressing tumors had 2.5 times increased levels of granulocytes in peripheral blood, which were also cytotoxic in vitro for W256 carcinoma cells. However, blood levels of cytokine-induced neutrophil chemoattractant-2, tumor necrosis factor α and interleukin 6 were similar between rats with regressing tumors and control healthy rats, suggesting that the observed regression of W256 carcinoma was caused by specific anticancer effects of the applied granulocytes. Anticancer effects of granulocytes were also found in BALBc mice bearing solid form of EAT, resulting in a 20% increase of survival in EAT-bearing mice. Therefore, the administration of granulocytes, isolated from healthy animals and applied at the site of solid tumors in rats and in mice, reduced experimental tumor growth, and extended the survival of tumor-bearing animals, while in some rats it even caused a W256 regression.
Jaganjac
Morana
M
Department of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, HR-10002 Zagreb, Croatia. Morana.Jaganjac@irb.hr
Poljak-Blazi
Marija
M
Kirac
Iva
I
Borovic
Suzana
S
Joerg Schaur
Rudolf
R
Zarkovic
Neven
N
D000818:Animals; D002279:Carcinoma 256, Walker / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002286:Carcinoma, Ehrlich Tumor / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019743:Chemokines, CXC / Q000097:blood; D006098:Granulocytes / Q000276:immunology* / Q000637:transplantation; D016219:Immunotherapy, Adoptive / Q000379:methods; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D019743:Chemokines, CXC; C513294:Cxcl3 protein, rat; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha