What question did this study set out to answer?

This research aims to explore how the microbial burden within tumors affects immune responses and interferon signaling in cancer, particularly colorectal and gastric cancers.

June 28, 2026Open Access

Tumor microbial burden drives immune responses through regulation of Interferon signaling

Key Points

This research aims to explore how the microbial burden within tumors affects immune responses and interferon signaling in cancer, particularly colorectal and gastric cancers.
Analyzed intratumoral microbial burden across various cancers with focus on CRC and STAD.
Investigated immune pathway activation through single-cell sequencing and immune checkpoint blockade in murine models.
Compared microbial burden in mismatch repair deficient and proficient tumor models.
High intratumoral microbial burden in CRC leads to increased interferon signaling and better outcomes in advanced cases.
Rectal MMRd cohort showed 100% remission after immune checkpoint blockade, correlating with increased microbial presence.
Depletion of local tumor microbes reduced immunotherapy efficacy and interferon signaling in murine models.

Abstract

Abstract Tumor microbes are increasingly recognized for modulating tumor behavior and therapy responses. Intratumoral microbial burden (ITMB) analysis across cancers revealed regulation of immune pathways, and activated mast cells, mostly in colorectal (CRC) and gastric (STAD) cancers. High ITMB CRC leads to interferon regulation and is associated with improved outcomes in advanced disease. Single-cell sequencing revealed induction of interferon-related genes (IRGs) within microbes-containing human CRC. GI-luminal mismatch repair deficiency (MMRd) tumors had higher ITMB than proficient tumors (MMRp). In a rectal MMRd cohort with 100% remission after immune checkpoint blockade (ICB), tumor microbes and microbes-containing mast cells increased. In ICB-sensitive syngeneic murine MMRd tumor models, local tumor microbial depletion, impaired ICB efficacy while downregulating IFN signaling. Forced upregulation of IRGs in ADAR1-deficient cancer cells restored immunotherapy responses during microbial ablation. These data highlight dynamic interplay between ITMB, host defense, and immunogenicity which seems key to determine therapy responses

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Cite This Study

Liu et al. (Fri,) studied this question.

synapsesocial.com/papers/6a40ba8861bb0a67205c6602 https://doi.org/https://doi.org/10.1158/2159-8290.cd-24-1908

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