Fig. 1

Primary, secondary, and tertiary interactions between the tumor and microbial communities. a Primary interactions are the interactions within the proximal tumor microenvironment. These interactions are important for understanding the mechanisms of microbiome-cancer relationships, such as tumorigenesis through specific microbes or bacterial proliferation in the tumor microenvironment. b Secondary interactions are the interactions between tumors and the microbial community of the tissue or organ system within the same general compartment. These interactions are mostly relevant for discerning potential biomarkers for screening. In this figure, the example is digesta passing by neoplastic tissue in the gut. The digesta may pick up some of the microbes from the tumor, which can be used as a signal of the tumor. Depending on the type and location of the tumor, these interactions may be more or less useful. Generally, an advantage to these interactions is ready access to the material for diagnosis. c Tertiary interactions are interactions between a tumor and a remote microbiome community. Tertiary interactions are less direct than secondary or primary interactions; they include therapeutic modulation by modifying chemotherapy drugs and reduce or increase effectiveness or toxicity, or immune modulation that leads to relevant immune cell differentiation or reaction, or metabolites that regulate hormones or host metabolism that can affect cancer phenotypes or outcomes. In spite of the physical distance and separate organ systems these microbial communities occupy relative to the tumor, they can have a profound effect on the tumor phenotype, treatment, and outcomes