Summary
Background and Significance
Converting “Cold tumors,” which respond poorly to cancer immunotherapy, into highly responsive “Hot tumors” is an urgent challenge in cancer treatment.
In recent years, “intratumoral bacteria”—bacteria residing within tumor tissue—have attracted considerable attention. The tumor interior is a unique microenvironment characterized by hypoxia, acidity, and nutrient restriction, and these bacteria are thought to have acquired distinct functions under selective pressures different from those of the gut microbiota.
Focus of the Study
In particular, the membrane vesicles (MVs) produced by bacteria can transport nucleic acids, proteins, lipids, and other molecules to host cells and thereby regulate immune responses. However, the functions of MVs derived from intratumoral bacteria remain almost entirely unexplored worldwide.
Research Plan
In this study, we will isolate intratumoral bacteria from clinical colorectal cancer specimens obtained from Japanese patients and comprehensively recover and analyze the MVs they produce.
Furthermore, we will evaluate the capacity of these MVs to induce dendritic cell and T cell responses, identify bacteria and MVs with immunostimulatory potential, and elucidate their cargo molecules and mechanisms of action.
Finally, using in vivo models, we will examine whether candidate MVs can remodel the tumor immune microenvironment and enhance the efficacy of immune checkpoint inhibitors.
Expected Outcome
Through this research, we aim to elucidate a novel intratumoral bacteria–MV–immunity axis and to create a new form of cancer immunotherapy that contributes to overcoming cases refractory to immunotherapy.
Members
Principal Investigator