Role of trained innate immunity against mucosal cancer

Mucosal tissues are frequent targets of both primary and metastatic cancers. This has highlighted the significance of both innate and adaptive anti-cancer immunity at mucosal sites. Trained innate immunity (TII) is an emerging concept defined as enhanced reactivity of innate leukocytes long after a previous stimulation that induces prolonged epigenetic, transcriptional, and metabolic changes. Trained innate leukocytes can respond to heterologous targets due to their lacking of antigen-specificity in most cases. Emerging experimental and clinical data suggest that certain microbes or their products induce TII in mucosal-associated innate leukocytes which endows heterologous anti-tumor innate immunity, in both prophylactic and therapeutic scenarios. In this mini-review, we summarize updated findings on the significance of TII in mucosal cancers. We also attempt to raise a few key questions critical to our further understanding on the roles of TII in mucosal cancers, and to the potential application of TII as anti-cancer strategy.