Topic

Dr. Naoko Ohtani will talk about "Exploring the Gut Microbiota's Role in Cancer Development and Progression," particularly regarding the gut-liver axis-mediated mechanism of liver cancer development.

Summary

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have emerged as major contributors to hepatocellular carcinoma (HCC). However, the precise mechanisms of how liver cancer develops in steatotic conditions remain unclear.

Her group previously revealed that obesity-induced deoxycholic acid (DCA), a gut microbial metabolite, triggers a senescence-associated secretory phenotype (SASP) in hepatic stellate cells (HSCs), , a phenotype that senescent cells secrete a variety of inflammatory cytokines, chemokines, proteases, and so on. Additionally, lipoteichoic acid (LTA), a gram-positive gut microbial component, enhances SASP via Toll-like receptor 2 activation.

IL-33, highly expressed in liver tumor regions, particularly within senescent HSCs, in an IL-1β-dependent manner, plays a crucial role in HCC development. Their study uncovered a novel mechanism for SASP factor release, including IL-33 and IL-1β, via membrane pores formed by gasdermin D N-terminal domain, which is activated by LTA. The released IL-33 suppresses antitumor immunity by activating ST2-positive Treg cells, contributing to MASH-related HCC progression.

In this symposium, Dr. Naoko Ohtani will further discuss their recent work on MASLD/MASH-associated HCC and highlight emerging insights into the gut microbiota's role in liver cancer development.

References:  (1) Yoshimoto et al. 499:97-101, Nature, 2013, (2) Loo et al. 7:522-538, Cancer Discovery, 2017, (3) Yamagishi et al. Science Immunology, 7, 2022, doi:10.1126/sciimmunol.abl7209.

About Dr. Naoko Ohtani

Dr. Naoko Ohtani is a Professor in the Department of Pathophysiology at Osaka Metropolitan University Graduate School of Medicine. She earned her M. D. from Kyoto Prefectural University of Medicine (KPUM) and later obtained her Ph.D. in 1995.

She conducted postdoctoral research at the CRUK Manchester Institute until 2003 before returning to Japan, where she held positions at Tokushima University, the Japanese Foundation for Cancer Research, and Tokyo University of Science. Since April 2017, she has been a Professor at Osaka Metropolitan University (formerly Osaka City University).

Her research focuses on the tumor microenvironment in liver cancer, with an emphasis on the gut-liver axis-mediated mechanism triggered by gut microbiota.

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