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Commensal Clostridiales strains mediate effective anti-cancer immune response against solid tumors
Cell Host & Microbe  (IF21.023),  Pub Date : 2021-08-27, DOI: 10.1016/j.chom.2021.08.001
Ana Montalban-Arques, Egle Katkeviciute, Philipp Busenhart, Anna Bircher, Jakob Wirbel, Georg Zeller, Yasser Morsy, Lubor Borsig, Jesus F. Glaus Garzon, Anne Müller, Isabelle C. Arnold, Mariela Artola-Boran, Michael Krauthammer, Anna Sintsova, Nicola Zamboni, Gabriel E. Leventhal, Laura Berchtold, Tomas de Wouters, Michael Scharl

Despite overall success, T cell checkpoint inhibitors for cancer treatment are still only efficient in a minority of patients. Recently, intestinal microbiota was found to critically modulate anti-cancer immunity and therapy response. Here, we identify Clostridiales members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC). Interestingly, these commensal species are also significantly reduced in CRC patients compared with healthy controls. Oral application of a mix of four Clostridiales strains (CC4) in mice prevented and even successfully treated CRC as stand-alone therapy. This effect depended on intratumoral infiltration and activation of CD8+ T cells. Single application of Roseburia intestinalis or Anaerostipes caccae was even more effective than CC4. In a direct comparison, the CC4 mix supplementation outperformed anti-PD-1 therapy in mouse models of CRC and melanoma. Our findings provide a strong preclinical foundation for exploring gut bacteria as novel stand-alone therapy against solid tumors.