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CCCZ Science Highlight: Commensal clostridiales strains mediate effective anti-cancer immune response against solid tumors

26. Oktober 2021

Cell host microbe

Montalban-Arques A, Katkeviciute E, Busenhart P, Bircher A, Wirbel J, Zeller G, Morsy Y, Borsig L, Glaus Garzon JF, Müller A, Arnold IC, Artola-Boran M, Krauthammer M, Sintsova A, Zamboni N, Leventhal GE, Berchtold L, de Wouters T, Rogler G, Baebler K, Schwarzfischer M, Hering L, Olivares-Rivas I, Atrott K, Gottier C, Lang S, Boyman O, Fritsch R, Manz MG, Spalinger MR, Scharl M. *CCCZ Members in bold

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.

Clostridialesbacteria strains that aresignificantly reduced in colorectal cancer patients compared with healthy individuals are effective in driving a potent anti-tumor response in solid tumors. This effect is mediated via activation of CD8+ T cells, independently of anti-PD-1 immunotherapy.
Clostridialesbacteria strains that aresignificantly reduced in colorectal cancer patients compared with healthy individuals are effective in driving a potent anti-tumor response in solid tumors. This effect is mediated via activation of CD8+ T cells, independently of anti-PD-1 immunotherapy.

Cell Host Microbe. 2021 Aug 25:S1931-3128(21)00377-2. doi: 10.1016/j.chom.2021.08.001.

Verantwortlicher Fachbereich

Comprehensive Cancer Center Zürich