- (Table S1) Control parameter values considered in the tumor-effector cell recruitment model - (Table S2) Parameter values estimated from the set of experiments corresponding to infection loads of 10^3 bacteria. - (Table S3) Parameter values estimated from the set of experiments corresponding to infection loads of5Ã-10^6 bacteria. - (Table S4) Parameter values estimated from the set of experiments corresponding to TNF-alpha administration. - (Table S5) Parameter values estimated from the set of experiments corresponding to infection loads of 10^3 bacteria and TNF-alpha administration. - (Figure S1) Long-term tumor control dependency on the initial number of effector cells E_0. - (Figure S2) Long-term tumor control dependency on the immune recruitment rate r.
ARTICLE ABSTRACT
Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor–effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553–63. ©2017 AACR.
