Turning tolerogenic into immunogenic ileal cell death through ileal microbiota: the key to unlock the mystery of colon cancer immunoscore?

Maria Paula Roberti; Marion Picard; Satoru Yonekura; Laurence Zitvogel

doi:10.1080/2162402X.2020.1778834

Turning tolerogenic into immunogenic ileal cell death through ileal microbiota: the key to unlock the mystery of colon cancer immunoscore?

Oncoimmunology. 2020 Jun 14;9(1):1778834. doi: 10.1080/2162402X.2020.1778834.

Authors

Maria Paula Roberti^{1

2

3}, Marion Picard^{1

2

4}, Satoru Yonekura^{1

2

5}, Laurence Zitvogel^{1

2

3

5

6}

Affiliations

¹ Gustave Roussy Cancer Campus (GRCC), UMR 1015, Villejuif, France.
² Institut National de la Santé et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale Contre le Cancer, Villejuif, France.
³ Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
⁴ Unit Biology and Genetics of the Bacterial Cell Wall, Institut Pasteur Paris, Paris, France.
⁵ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre cedex, France.
⁶ Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.

Abstract

Why PD-1 blockade is ineffective in the vast majority of colorectal cancers (CCs) lacking microsatellite instability but harboring high densities of tumor infiltrating T cells and follicular T helper (TFH) and B cells remained so far an open conundrum. In a recent report published in Nature Medicine, we bring evidence in mice and patients that ileal microbiota turns tolerogenic apoptosis of ileal intestinal epithelial cells (IEC) into immunogenic cell demise capable of eliciting IL-1β-dependent TFH responses that benefit from anti-PD1 antibodies.

Keywords: B. fragilis; Colon cancer; F. nucleatum; P. clara; ileum; immune checkpoint; immunity; microbiome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colonic Neoplasms* / genetics
Colorectal Neoplasms*
Humans
Immunogenic Cell Death
Mice
Microbiota*
Microsatellite Instability

Grants and funding

LZ was supported by the Ligue contre le Cancer (équipe labelisée); Agence Nationale de la Recherche (ANR) francogermanique ANR-19-CE15-0029, ANR Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); BMS Foundation, Cancéropôle Ile-de-France; Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; the European Commission (ArtForce); the European Research Council (ERC); Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumière (ANR-16-RHUS-0008); H2020 ONCOBIOME, the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); Groupe Dassault; Badinter philantropia, and the Paris Alliance of Cancer Research Institutes (PACRI).