Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity

Author(s):Show less -

Almeida, Rafael Ribeiro ^{[1, 2]} ; Vieira, Raquel de Souza ^{[1, 2]} ; Castoldi, Angela ^[1] ; Terra, Fernanda Fernandes ^[1] ; Melo, Amanda Campelo L. ^[1] ; Campos Canesso, Maria Cecilia ^[3] ; Lemos, Luisa ^[3] ; Cipelli, Marcella ^[1] ; Rana, Nisha ^[4] ; Hiyane, Meire Ioshie ^[1] ; Pearce, Erika L. ^[4] ; Martins, Flaviano dos Santos ^[5] ; Caetano de Faria, Ana Maria ^[3] ; Saraiva Camara, Niels Olsen ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Heart Inst INCOR, Lab Immunol, Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Biol Sci Inst, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil

^[4] Max Planck Inst Epigenet & Immunobiol, Dept Immunometab, Freiburg - Germany

^[5] Univ Fed Minas Gerais, Biol Sci Inst, Dept Microbiol, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: BRITISH JOURNAL OF CANCER; v. 123, n. 4 JUN 2020.
• Web of Science Citations: 2

Abstract

Background Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. Methods We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice. Results We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-beta gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice. Conclusions Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells. (AU)

• FAPESP's process: 15/13817-0 - The role of microbiota in the development of Th9 cells-mediated antitumor activity
• Grantee: Rafael Ribeiro Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral