Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer.
An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9)S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 x 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent.
Feltis
B A
BA
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
Miller
J S
JS
Sahar
D A
DA
Kim
A S
AS
Saltzman
D A
DA
Leonard
A S
AS
Wells
C L
CL
Sielaff
T D
TD
D000818:Animals; D000941:Antigens / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface; D001773:Blood Cells / Q000276:immunology / Q000473:pathology*; D017252:CD3 Complex / Q000032:analysis; D018938:Caco-2 Cells; D002478:Cells, Cultured; D020895:Enterocytes / Q000382:microbiology; D005260:Female; D019073:HT29 Cells; D006801:Humans; D037181:Lectins, C-Type; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008113:Liver Neoplasms / Q000382:microbiology* / Q000473:pathology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010641:Phenotype; D011506:Proteins / Q000032:analysis; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000473:pathology*; D012486:Salmonella typhimurium / Q000502:physiology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins