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. 2020 Jun 14;9(1):1778834.
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?

Maria Paula Roberti  1   2   3 , Marion Picard  1   2   4 , Satoru Yonekura  1   2   5 , Laurence Zitvogel  1   2   3   5   6
Affiliations

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

V体育2025版 - Maria Paula Roberti et al. Oncoimmunology. .

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 VSports手机版. .

Keywords: B. fragilis; Colon cancer; F V体育安卓版. nucleatum; P. clara; ileum; immune checkpoint; immunity; microbiome. .

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Figures

Figure 1.
Figure 1.
Proposed mechanism of action how the gut microbiota impacts the immunogenic apoptosis of ileal IEC during oxaliplatin based chemotherapy. Chemotherapy acts not only on the tumor cells but on dividing cells, in particular the IEC of the ileal crypts, resulting in their Casp3-deficient cell death. The immunogenic potential of IEC death relies on the profile of the ileal microbiota. Local immunity is then modulated by migration of CD103+CD11b− (Batf3+) DCS to the mLN where they trigger a local immune response characterized by the IL-1β and IL-12 dependent activation of TFH cells. TFH accumulate in the tumor microenvironment and shift the balance toward anti-tumor immunity in colorectal cancer, restoring responsiveness to PD-1 blockade.
See this image and copyright information in PMC

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