Interactions between microbiota and innate immunity in tumor microenvironment: Novel insights into cancer progression and immunotherapy

Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites, influencing both physiological and pathological states. In individuals with a genetic predisposition, disruptions to the “innate immunity‒microbiota” axis appear to rewire immune responses within the tumor microenvironment (TME), thereby driving cancer pathogenesis. This review summarizes the intricate crosstalk between the microbiota and innate immunity in both healthy and cancerous states, focusing on the modulation of immune recognition and polarization during tumor progression, including immune escape, barrier disruption, chronic inflammatory transformation, and angiogenesis in the initiation phase, as well as the regulation of local invasion, vascular invasion, and pre-metastatic ecological niche formation involved in the metastatic phase. This review also highlights recent advances and challenges in leveraging microbiota for cancer immunotherapy, covering innovations in bacteriophages, genetically engineered probiotics, and bioinformatic applications. Moreover, this review proposes potential approaches to enhance therapeutic efficacy by targeting innate immunity‒microbiota interactions. Further mechanistic insights into these interactions may pave the way for developing innovative microbiota-based cancer immunotherapies.