Tumor-associated bacterial effectors: novel frontiers in tumor biology and immunity

The complex and dynamic bacterial community symbiotically interacts with the host in many body niches and participates in various physiological and pathological states, including cancer. Advances in biotechnology have shifted the research focus from merely profiling bacterial abundance to identifying the functionally relevant bacteria-derived effectors that modulate tumor biology and immune responses. Here, we introduce a conceptual classification framework designating these effectors as tumor-associated bacterial effectors (TABEs), aiming to consolidate and direct ongoing investigations. Under this proposed taxonomy, TABEs can be classified into six distinct categories: virulence factors, microorganism-associated molecular patterns (MAMPs), bacterial metabolites, biotransformative enzymes, cross-reactive antigens, and noncoding RNAs (ncRNAs). We comprehensively summarize their functional mechanisms and multifaceted roles in tumor progression and immunomodulation. Based on these insights, we propose multidimensional potential therapeutic strategies targeting TABEs. Furthermore, we discuss current limitations that warrant further investigations and emerging trends that may shape future research directions in this field. Collectively, in-depth investigations of TABEs may help elucidate the complex human-bacteria crosstalk and expand the paradigm of tumor biology and immunity.