Bacterial colibactin-induced lipid accumulation and loss of a c-type lectin cooperates for supporting an immune-suppressive microenvironment in right-sided colon cancer

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de Oliveira Alves, Nilmara | Vaysse, Amaury | Dalmasso, Guillaume | Nikitina, Darja | Boulard, Olivier | Sauvanet, Pierre | Poulin, Lionel Franz | Kennedy, Sean, P | Sobhani, Iradj | Bonnet, Richard | Chamaillard, Mathias

Edité par CCSD -

International audience. Right-sided colon cancer (RCC) patients exhibit difference in the microbiota organization in relation to left-sided colon cancer and has a worse prognosis. Among several species of bacteria associated with colon cancer, colibactin-producing by Escherichia coli (CoPEC) are attracting attention. However, if CoPEC contributes to tumor lipid metabolism remains incompletely understood. Herein, we revealed that CoPEC is negatively correlated with human regenerating family member 3 alpha gene (REG3A) expression and trigger reprogramming lipid metabolism, which exacerbates accumulation of glycerophospholipids. Notably, APC mutation and metabolic consensus molecular subtype (CMS3) are predominant in RCC, especially in patients colonized by CoPEC. While SFRP2 expression is increased in these tumors, CD8+ T cells were reduced. In addition, human tumors have similarities to mice tumors. In particular, mRNAs encoding immunoglobulins heavy chains were clearly increased in both models with low Reg3A expression. Taken together, CoPEC associated with REG3A is promising as a biomarker in cancer therapy.

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