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. 2021 Oct 13;29(10):1573-1588.e7.
doi: 10.1016/j.chom.2021.08.001. Epub 2021 Aug 27.

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

Ana Montalban-Arques  1 , Egle Katkeviciute  1 , Philipp Busenhart  1 , Anna Bircher  1 , Jakob Wirbel  2 , Georg Zeller  2 , Yasser Morsy  1 , Lubor Borsig  3 , Jesus F Glaus Garzon  3 , Anne Müller  4 , Isabelle C Arnold  4 , Mariela Artola-Boran  4 , Michael Krauthammer  5 , Anna Sintsova  5 , Nicola Zamboni  6 , Gabriel E Leventhal  7 , Laura Berchtold  8 , Tomas de Wouters  8 , Gerhard Rogler  1 , Katharina Baebler  1 , Marlene Schwarzfischer  1 , Larissa Hering  1 , Ivan Olivares-Rivas  1 , Kirstin Atrott  1 , Claudia Gottier  1 , Silvia Lang  1 , Onur Boyman  9 , Ralph Fritsch  10 , Markus G Manz  10 , Marianne R Spalinger  1 , Michael Scharl  11
Affiliations

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

Ana Montalban-Arques et al. Cell Host Microbe. .

Abstract

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.

Keywords: Clostridiales; cancer; colorectal cancer; gut microbiota; immunotherapy; solid tumors; tumor models; tumor therapy.

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Conflict of interest statement

Declaration of interests M.S. and M.R.S. have shares in PharmaBiome. M.S. served as Advisor for Gilead, Fresenius, Topadur, Takeda, and Celltrion, and received speaker’s honoraria from Falk Pharma and Vifor Pharma. T.W. and L. Berchtold are employees of PharmaBiome. G.E.L. is also an employee of PharmaBiome. G.R. is member of the Board of Directors of PharmaBiome. A patent related to this work has been generated (PCT/EP2021/053390). This intellectual property is entirely owned by the University of Zürich.

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