Intracellular bacteria in cancer—prospects and debates

Recent evidence suggests that some human cancers may harbor low-biomass microbial ecosystems, spanning bacteria, viruses, and fungi. Bacteria, the most-studied kingdom in this context, are suggested by these studies to localize within cancer cells, immune cells and other tumor microenvironment cell types, where they are postulated to impact multiple cancer-related functions. Herein, we provide an overview of intratumoral bacteria, while focusing on intracellular bacteria, their suggested molecular activities, communication networks, host invasion and evasion strategies, and long-term colonization capacity. We highlight how the integration of sequencing-based and spatial techniques may enable the recognition of bacterial tumor niches. We discuss pitfalls, debates and challenges in decisively proving the existence and function of intratumoral microbes, while reaching a mechanistic elucidation of their impacts on tumor behavior and treatment responses. Together, a causative understanding of possible roles played by intracellular bacteria in cancer may enable their future utilization in diagnosis, patient stratification, and treatment.