B cells are required for tumor-targeting Salmonella in host

Abstract

Systemic administration of Salmonella to tumor-bearing mice leads to the preferential accumulation within tumor sites and retardation of the tumor growth. Host factors including innate and adaptive immune responses influence Salmonella-induced antitumor activity. Antitumor activities of Salmonella are not only determined by the tumor regression but also by the host immune response. Herein, we demonstrated that B cells play an important role in the antitumor activity mediated by Salmonella. Body weight and survival of B cell-deficient mice were decreased compared with wild-type, CD8(+) cell-deficient, or CD4(+) cell-deficient mice after Salmonella administration. Although Salmonella accumulated within the tumors in B cell-deficient mice, the bacterial loads of healthy organs were higher than those in wild-type mice. The inflammation cytokine and bacteremia were found in B cell-deficient mice after Salmonella treatment. When Salmonella accumulated within the tumor, B cells inhibited the dissemination of Salmonella to other healthy organs. The depletion of host B cells resulted in a noticeably higher total number of Salmonella in the tumor and inhibited tumor growth. Meanwhile, B cell-depletive and B cell-adoptive transfer of serum experiments demonstrated that the natural antibody produced by B cell takes part in the control of Salmonella dissemination in tumor-bearing mice. In this study, we want to address the mechanisms of incorporating host immunoresponse as a way to augment the antitumor activities of Salmonella.

Salmonella as an Innovative Therapeutic Antitumor Agent

“…The inflammation cytokines and bacteremia were found in B cell-deficient mice after Salmonella treatment. When Salmonella accumulated within the tumor, B cells inhibited the dissemination of Salmonella to other healthy organs [23]. A major source of natural antibodies seems to be the B-1 cell subset.…”

Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by Triptolide and Its Mechanism

“…The host immune response is one of the key factors that modulate Salmonella's antitumour effects 7-9. Salmonella triggers a cascade of cellular signalling events, including NFκB signalling, immediately upon its entry into the body, leading to the release of cytokines and chemokines, which recruit polymorphonuclear cells 10.…”

“…Salmonella triggers a cascade of cellular signalling events, including NFκB signalling, immediately upon its entry into the body, leading to the release of cytokines and chemokines, which recruit polymorphonuclear cells 10. These inflammatory cells play different roles in Salmonella -colonized tumours 8, 9, 11. Neutrophils directly cause the elimination of bacteria from the body 8, 11, while CD8 + T cells contribute to the tumour growth suppression effect of Salmonella 12, 13.…”

Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR pathway

“…This rough variant of S.C., which is designated vaccine 51, was obtained by spreading an 18-hour broth culture of the virulent strain 188 of the S. Choleraesuis serovar Dublin over the surface of a dried nutrient agar plate, adding a drop of a suspension of salmonella anti-o phage No. 1 and selecting for a phage-resistant colony after incubation at 37 1C for 24 h 27,28. Murine K1735, 29 B16F10 30,31 melanoma cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 50 mg ml À 1 gentamicin, 2 mM L-glutamine and 10% heat-inactivated fetal bovine serum at 37 1C in 5% CO 2 .…”