Bacteria-based immunotherapy for cancer: A systematic review of preclinical studies Original paper

What was studied?

This review focuses on bacteria-based immunotherapy for cancer, which has emerged as a novel strategy leveraging the immune-modulatory properties of bacteria to fight cancer. The paper explores various preclinical studies assessing the potential of bacteria, bacterial components, and bacterial derivatives in modulating immune responses to induce tumor-specific immunity. The review examines the roles of different bacterial species, such as Salmonella, Escherichia coli, and Listeria, in enhancing the effectiveness of cancer immunotherapy. It also highlights the mechanisms through which bacteria act as immune adjuvants, stimulating immune cells to attack cancer cells directly or to reverse the immunosuppressive tumor microenvironment (TME).

Who was studied?

The review synthesizes data from a variety of preclinical studies across multiple cancer types, including colorectal cancer, melanoma, breast cancer, and pancreatic cancer. The studies include animal models such as mice, with various tumors being used to evaluate the impact of bacteria-based therapies. The immune cells involved in these studies include macrophages, dendritic cells, natural killer (NK) cells, and T cells, all of which play critical roles in the activation of antitumor immunity. Additionally, the review assesses the efficacy of combining bacterial treatments with other cancer therapies, including chemotherapy, immune checkpoint inhibitors (ICIs), and photodynamic therapy.

Most important findings

The review identifies several key insights into the use of bacteria in cancer immunotherapy. First, it highlights how bacteria, such as Salmonella and E. coli, can be engineered to target tumor cells, promoting immune cell activation and tumor regression. Bacteria can also help reverse immune tolerance by downregulating immune checkpoints, such as PD-L1, making them potent partners in combination with immune checkpoint inhibitors (ICIs). For example, Salmonella has been shown to enhance the effectiveness of PD-L1 blockade in colorectal cancer models. The paper further discusses bacterial outer membrane vesicles (OMVs), bacterial flagellin, and bacterial-derived toxins, all of which act as immune adjuvants by activating immune cells, including T cells and NK cells, to enhance tumor killing. Notably, preclinical studies also suggest that combining bacteria-based therapies with other conventional therapies, such as chemotherapy and photodynamic therapy, results in enhanced therapeutic outcomes.

Key implications

The findings underscore the potential of bacteria-based therapies as a promising adjunct to current cancer treatments. By utilizing bacteria to stimulate the immune system and target tumors, researchers may overcome some of the limitations of traditional therapies, including immune suppression and treatment resistance. The ability to modify bacteria to express specific antigens or therapeutic proteins offers a customizable approach to cancer treatment. However, the review also highlights several challenges that need to be addressed before clinical translation, including concerns about bacterial toxicity, biosafety, and the need for standardized production methods. Future research must focus on optimizing bacterial delivery systems, ensuring safety in human trials, and further exploring the synergy between bacteria-based therapies and other forms of immunotherapy.