Resolving the Paradox of Colon Cancer Through the Integration of Genetics, Immunology, and the Microbiota.
Animals
Antineoplastic Agents
/ therapeutic use
Bacteria
/ immunology
Biomarkers, Tumor
/ genetics
Colon
/ drug effects
Colonic Neoplasms
/ genetics
Dysbiosis
Gastrointestinal Microbiome
/ drug effects
Gene Expression Regulation, Neoplastic
Host-Pathogen Interactions
Humans
Immunity, Cellular
Immunity, Humoral
Lymphocytes, Tumor-Infiltrating
/ immunology
Prognosis
Tumor Escape
Tumor Microenvironment
Bacteroides fragilis
Fusobacterium nucleatum
colon cancer
ileum
immune checkpoint
immunity
microbiome
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
08
2020
accepted:
09
11
2020
entrez:
31
12
2020
pubmed:
1
1
2021
medline:
22
6
2021
Statut:
epublish
Résumé
While colorectal cancers (CRC) are paradigmatic tumors invaded by effector memory lymphocytes, the mechanisms accounting for the relative resistance of MSI negative CRC to immunogenic cell death mediated by oxaliplatin and immune checkpoint inhibitors has remained an open conundrum. Here, we propose the viewpoint where its microenvironmental contexture could be explained -at least in part- by macroenvironmental cues constituted by the complex interplay between the epithelial barrier, its microbial ecosystem, and the local immune system. Taken together this dynamic ménage-à-trois offers novel coordinated actors of the humoral and cellular immune responses actionable to restore sensitivity to immune checkpoint inhibition. Solving this paradox involves breaking tolerance to crypt stem cells by inducing the immunogenic apoptosis of ileal cells in the context of an ileal microbiome shifted towards immunogenic bacteria using cytotoxicants. This manoeuver results in the elicitation of a productive Tfh and B cell dialogue in mesenteric lymph nodes culminating in tumor-specific memory CD8
Identifiants
pubmed: 33381121
doi: 10.3389/fimmu.2020.600886
pmc: PMC7768083
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
600886Informations de copyright
Copyright © 2020 Fidelle, Yonekura, Picard, Cogdill, Hollebecque, Roberti and Zitvogel.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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