TIME for bugs: the immune microenvironment and microbes in pre-cancer.

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of pre-cancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further elucidate the premalignant immune microenvironment, but also for the utility of pharmacologic and lifestyle interventions to alter the immune microenvironment of early lesions to reverse carcinogenesis. Novel research methodologies, such as implementing spatial transcriptomics and proteomics, in combination with innovative sampling methods will advance precision targeting of the premalignant immune microenvironment. Additional studies defining the continuum of immune and microbiome evolution, which emerges in parallel with tumor development, will provide novel opportunities for cancer interception at the earliest steps in carcinogenesis.