Setting "cold" tumors on fire: Cancer therapy with live tumor-targeting bacteria

Immunotherapy with checkpoint blockade has shown remarkable efficacy in many patients with a variety of different types of cancer. However, the majority of patients with cancer have yet to benefit from this revolutionary therapy. Studies have shown that checkpoint blockade works best against immune-inflamed tumors characterized by the presence of tumor-infiltrating lymphocytes (TILs). In this review, we summarize studies using live tumor-targeting bacteria to treat cancer and describe various strategies to engineer the tumor-targeting bacteria for maximized immunoregulatory effects. We propose that tumor-localized infections by such engineered bacteria can create an immune microenvironment in favor of a more effective antitumor immunity with or without other therapies, such as immune checkpoint blockade (ICB). Finally, we will briefly outline some exemplary oncology clinical trials involving ICB plus live therapeutic bacteria, with a focus on their ability to modulate antitumor immune responses.