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Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

(2020) NATURE MEDICINE. 26(6). p.919-931
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Abstract
The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (T-FH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of T-FH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of T-FH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1(+) T-FH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC. Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.
Keywords
T-CELL RESPONSES, MICROSATELLITE INSTABILITY, COLORECTAL-CANCER, HELPER-CELLS, STEM-CELLS, IDENTIFICATION, SURVIVAL

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MLA
Roberti, Maria Paula, et al. “Chemotherapy-Induced Ileal Crypt Apoptosis and the Ileal Microbiome Shape Immunosurveillance and Prognosis of Proximal Colon Cancer.” NATURE MEDICINE, vol. 26, no. 6, 2020, pp. 919–31, doi:10.1038/s41591-020-0882-8.
APA
Roberti, M. P., Yonekura, S., Duong, C. P. M., Picard, M., Ferrere, G., Alou, M. T., … Zitvogel, L. (2020). Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. NATURE MEDICINE, 26(6), 919–931. https://doi.org/10.1038/s41591-020-0882-8
Chicago author-date
Roberti, Maria Paula, Satoru Yonekura, Connie P. M. Duong, Marion Picard, Gladys Ferrere, Maryam Tidjani Alou, Conrad Rauber, et al. 2020. “Chemotherapy-Induced Ileal Crypt Apoptosis and the Ileal Microbiome Shape Immunosurveillance and Prognosis of Proximal Colon Cancer.” NATURE MEDICINE 26 (6): 919–31. https://doi.org/10.1038/s41591-020-0882-8.
Chicago author-date (all authors)
Roberti, Maria Paula, Satoru Yonekura, Connie P. M. Duong, Marion Picard, Gladys Ferrere, Maryam Tidjani Alou, Conrad Rauber, Valerio Iebba, Christian H. K. Lehmann, Lukas Amon, Diana Dudziak, Lisa Derosa, Bertrand Routy, Caroline Flament, Corentin Richard, Romain Daillere, Aurelie Fluckiger, Isabelle Van Seuningen, Mathias Chamaillard, Audrey Vincent, Stephanie Kourula, Paule Opolon, Pierre Ly, Eugenie Pizzato, Sonia Becharef, Juliette Paillet, Christophe Klein, Florence Marliot, Filippo Pietrantonio, Stephane Benoist, Jean-Yves Scoazec, Peggy Dartigues, Antoine Hollebecque, David Malka, Franck Pages, Jerome Galon, Ivo Gomperts Boneca, Patricia Lepage, Bernard Ryffel, Didier Raoult, Alexander Eggermont, Tom Vanden Berghe, Francois Ghiringhelli, Peter Vandenabeele, Guido Kroemer, and Laurence Zitvogel. 2020. “Chemotherapy-Induced Ileal Crypt Apoptosis and the Ileal Microbiome Shape Immunosurveillance and Prognosis of Proximal Colon Cancer.” NATURE MEDICINE 26 (6): 919–931. doi:10.1038/s41591-020-0882-8.
Vancouver
1.
Roberti MP, Yonekura S, Duong CPM, Picard M, Ferrere G, Alou MT, et al. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. NATURE MEDICINE. 2020;26(6):919–31.
IEEE
[1]
M. P. Roberti et al., “Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer,” NATURE MEDICINE, vol. 26, no. 6, pp. 919–931, 2020.
@article{8665032,
  abstract     = {{The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (T-FH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of T-FH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of T-FH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1(+) T-FH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC. Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.}},
  author       = {{Roberti, Maria Paula and Yonekura, Satoru and Duong, Connie P. M. and Picard, Marion and Ferrere, Gladys and Alou, Maryam Tidjani and Rauber, Conrad and Iebba, Valerio and Lehmann, Christian H. K. and Amon, Lukas and Dudziak, Diana and Derosa, Lisa and Routy, Bertrand and Flament, Caroline and Richard, Corentin and Daillere, Romain and Fluckiger, Aurelie and Van Seuningen, Isabelle and Chamaillard, Mathias and Vincent, Audrey and Kourula, Stephanie and Opolon, Paule and Ly, Pierre and Pizzato, Eugenie and Becharef, Sonia and Paillet, Juliette and Klein, Christophe and Marliot, Florence and Pietrantonio, Filippo and Benoist, Stephane and Scoazec, Jean-Yves and Dartigues, Peggy and Hollebecque, Antoine and Malka, David and Pages, Franck and Galon, Jerome and Boneca, Ivo Gomperts and Lepage, Patricia and Ryffel, Bernard and Raoult, Didier and Eggermont, Alexander and Vanden Berghe, Tom and Ghiringhelli, Francois and Vandenabeele, Peter and Kroemer, Guido and Zitvogel, Laurence}},
  issn         = {{1078-8956}},
  journal      = {{NATURE MEDICINE}},
  keywords     = {{T-CELL RESPONSES,MICROSATELLITE INSTABILITY,COLORECTAL-CANCER,HELPER-CELLS,STEM-CELLS,IDENTIFICATION,SURVIVAL}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{919--931}},
  title        = {{Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer}},
  url          = {{http://dx.doi.org/10.1038/s41591-020-0882-8}},
  volume       = {{26}},
  year         = {{2020}},
}

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