Bacteria in cancer therapy: beyond immunostimulation

Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery have increased survival significantly. New therapies have arisen with the same goal; immunotherapy has appeared as a promising option in the fight against cancer stimulating the immune system by inducing innate and adaptive responses. These responses include release of pro-inflammatory cytokines, making the immune system capable to eliminate or protect against multiple tumors. Nowadays, many of these therapies are being used in clinical settings, such as checkpoint inhibitors, monoclonal anti cytotoxic T-Lymphocyte associated protein 4 (CTL-4) and programmed death protein 1 (PD1), with inspiring results; however, they may decrease immunotolerance, limiting their use. At the same time, chemotherapy works by passive transport across the cell membrane, limiting its capacity to penetrate in tumor cells. For these reasons, bacteria employment represents one of the best candidates for cancer treatment. They can surpass these barriers with their selective colonization which also has an oncolytic effect by increasing proliferation and immunostimulation in the tumor environment. Attenuated strains, such as Mycobacterium bovis, Clostridium, Salmonella typhimirium and Listeria monocytogenes have been studied showing promising results in experimental models. However, their application in clinical trials has shown the need to maximize their therapeutic effect. Genetic engineering and synthetic biology are necessary to prove the scope that this novel approach has against cancer due to implications of cancer therapy and public health.