Immune cell composition and immune cell-bacteria interactions differ between colorectal cancer tumors and adjacent tissue, with bacterial LPS showing altered colocalization patterns with distinct immune cell subsets in CRC compared to paired adjacent intestinal tissue.
Key Findings
Results
Bacterial LPS accumulates regionally in colorectal cancer tissue and colocalizes with distinct immune cell subsets, with different patterns observed in CRC versus adjacent tissue.
The study applied 3D light-sheet imaging, spatial transcriptomics, and imaging mass cytometry to patient-derived CRC and adjacent intestinal tissue
Bacterial LPS was visualized alongside immune cells and vessels using these multimodal imaging approaches
Regional bacterial LPS accumulation and colocalization with distinct immune cell subsets was identified in both tissue types
The spatial distribution of bacteria and their interactions with immune cells in CRC tumors was previously poorly understood
Results
In CRC-adjacent tissue, bacterial LPS is mainly associated with CD11c+ dendritic cells, CD15+ neutrophils, and CD163+ macrophages.
Three primary immune cell populations were identified as LPS-associated in adjacent intestinal tissue: CD11c+ dendritic cells, CD15+ neutrophils, and CD163+ macrophages
This pattern represents the homeostatic crosstalk between bacterial LPS and immune cells in tissue adjacent to the tumor
These findings were derived from patient-derived paired tissue samples allowing direct comparison between tumor and adjacent tissue
Results
In matched CRC tissue, the number of CD163+ macrophages and CD11c+ dendritic cells and their colocalization with LPS decreased compared to adjacent tissue.
Both the absolute number of CD163+ macrophages and CD11c+ dendritic cells were reduced in CRC tumor tissue
The colocalization of these cell types with bacterial LPS also decreased in CRC tissue relative to paired adjacent tissue
This reduction suggests an altered innate immune surveillance mechanism in the tumor microenvironment
Matched/paired tissue design allowed direct comparison between each patient's tumor and their own adjacent intestinal tissue
Results
CD15+ neutrophils and their colocalization with LPS increased in CRC tumor tissue compared to adjacent intestinal tissue.
While CD163+ macrophages and CD11c+ dendritic cells decreased, CD15+ neutrophils showed an opposite pattern of increase in CRC tissue
The colocalization of CD15+ neutrophils with bacterial LPS was also increased in CRC compared to adjacent tissue
This shift suggests a fundamentally altered immune cell composition and host-microbiota interaction in the tumor microenvironment
Background
CRC is characterized by an imbalance in bacterial composition and bacterial translocation across the intestinal barrier that disrupts normal immune-microbiota homeostasis.
Under homeostatic conditions, the gut microbiota is tightly regulated by interactions with the mucosal immune system
CRC disrupts this regulation, leading to altered bacterial composition and translocation
The study used patient-derived CRC and paired adjacent intestinal tissue to capture these differences within the same individuals
The findings offer insights into host-microbiota dynamics and mechanistic interactions in the context of colorectal cancer
What This Means
This research suggests that the relationship between gut bacteria and immune cells is fundamentally different inside colorectal cancer tumors compared to the nearby healthy intestinal tissue in the same patients. Using advanced imaging technologies including 3D light-sheet imaging, spatial transcriptomics, and imaging mass cytometry, the researchers were able to map exactly where bacterial lipopolysaccharide (LPS, a component of bacterial cell walls) was located in tissue samples and which immune cells were in close proximity to it. In healthy-adjacent tissue, LPS was primarily found near dendritic cells and macrophages — cell types that are typically involved in recognizing and responding to bacteria in a controlled way — as well as neutrophils. Inside the tumors, however, the macrophages and dendritic cells were fewer in number and less associated with LPS, while neutrophils became more numerous and more closely associated with LPS.
This shift matters because macrophages and dendritic cells are important for orchestrating adaptive immune responses and maintaining tolerance to commensal bacteria, while neutrophils are more associated with acute inflammatory responses. The finding that CRC tumors show reduced macrophage and dendritic cell engagement with bacterial LPS, alongside increased neutrophil-LPS interactions, suggests the tumor microenvironment may be undermining normal immune surveillance and reshaping how the immune system responds to the bacteria present. This research suggests that the altered crosstalk between bacteria and immune cells in colorectal cancer tumors may contribute to the immunosuppressive or pro-tumorigenic environment often observed in these cancers, and that understanding these spatial interactions could provide new insights into how tumors evade immune control.
Walberg &, Reuss A, Ziadlou R, Mamie C, Gottier C, White A, et al.. (2026). Altered crosstalk of bacterial lipopolysaccharide with immune cells in colorectal cancer compared to paired adjacent intestinal tissue.. Gut microbes. https://doi.org/10.1080/19490976.2026.2665878