Therapeutic Potential of Bacteria against Solid Tumors

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. .

Immunologic Consequences of Sequencing Cancer Radiotherapy and Surgery

“…Different mathematical models have been proposed to simulate tumor-immune system interactions 21,22,[49][50][51][52][53][54][55][56][57][58][59] and the synergistic effects of radiotherapy with the immune system and immunotherapy. 22,[60][61][62][63] To demonstrate immunologic consequences of sequencing radiotherapy and surgery, we extended the established Kuznetsov model and its parameterization as previously discussed.…”

Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition

“…When Salmonella was administrated into the solid tumor within hemorrhagic area, the bacteria will proliferate and consume the oxygen and nutrients, leading to necrotic regions of hemorrhaging area, destroy the blood vessels, and finally reduce the proliferation of tumor cells [34,124]. Most bacteria have the ability to attack and colonize cancer cells, and in best cases, this leads to the treatment of cancer completely [132][133][134].…”

“…When Salmonella was administrated into the solid tumor within hemorrhagic area, the bacteria will proliferate and consume the oxygen and nutrients, leading to necrotic regions of hemorrhaging area, destroy the blood vessels, and finally reduce the proliferation of tumor cells [ 34 , 124 ]. Most bacteria have the ability to attack and colonize cancer cells, and in best cases, this leads to the treatment of cancer completely [ 132 – 134 ]. The recent studies demonstrated that the microbiome within the human body targeted the tumor cells because of decreased immune activity in the necrotic cores of tumor [ 135 ]; some bacteria can grow into tumors that are preferred for reproduction by consuming food and oxygen, causing cancer cells to starve and suffocate.…”

Modeling and Analyzing Stem-Cell Therapy toward Cancer: Evolutionary Game Theory Perspective

“…The dynamics of targeted cancer therapy have been investigated using a mathematical model of somatic evolution (19). Bacteria and/or pro-inflammatory cytokine TNF in a set of established murine modes of cancer was presented in (20). An agent-based method of immune and epithelial cell interactions in breast lobular epithelium was developed to earn perspicacity towards the prognostic potential of inflammation (21).…”