Commensal Clostridiales strains mediate effective anti-cancer immune response against solid tumors

• Published in: Cell host & microbe Vol. 29; no. 10; pp. 1573 - 1588.e7
• Main Authors: Montalban-Arques, Ana, Katkeviciute, Egle, Busenhart, Philipp, Bircher, Anna, Wirbel, Jakob, Zeller, Georg, Morsy, Yasser, Borsig, Lubor, Glaus Garzon, Jesus F., Müller, Anne, Arnold, Isabelle C., Artola-Boran, Mariela, Krauthammer, Michael, Sintsova, Anna, Zamboni, Nicola, Leventhal, Gabriel E., Berchtold, Laura, de Wouters, Tomas, Rogler, Gerhard, Baebler, Katharina, Schwarzfischer, Marlene, Hering, Larissa, Olivares-Rivas, Ivan, Atrott, Kirstin, Gottier, Claudia, Lang, Silvia, Boyman, Onur, Fritsch, Ralph, Manz, Markus G., Spalinger, Marianne R., Scharl, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.10.2021
• Subjects: Animals; Biological Therapy; cancer; CD8-Positive T-Lymphocytes - immunology; Clostridiales; Clostridiales - immunology; Clostridiales - physiology; colorectal cancer; Colorectal Neoplasms - immunology; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - therapy; Gastrointestinal Microbiome; gut microbiota; Humans; Immunity; immunotherapy; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; solid tumors; Symbiosis; tumor models; tumor therapy; colorectal cancer; tumor models; immunotherapy; Clostridiales; cancer; tumor therapy; gut microbiota; solid tumors
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2021.08.001

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. [Display omitted] •Clostridiales bacteria are associated with low tumor burden in colon cancer models•Selected Clostridiales bacteria are diminished in colorectal cancer patients•A mix of Clostridiales strains have a potent anti-tumor effect via CD8+ T cells•Clostridiales treatment is effective in solid tumors independently of anti-PD-1 Montalban-Arques et al. report that Clostridiales bacteria strains that are significantly reduced in colorectal cancer patients compared with healthy individuals are effective in driving a potent anti-tumor response in solid tumors. They demonstrate that this is via activation of CD8+ T cells, independently of anti-PD-1 immunotherapy.