188P - Single-cell and spatial transcriptomics delineate the microstructure and immune landscape of intrahepatic cholangiocarcinoma in the leading-edge area

Background

A thorough investigation of the tumor cells and immune microenvironment within the lead-edge area is essential for understanding the mechanisms behind the progression of ICC and devising a targeted therapy in the hope of providing clinical benefits for patients.

Methods

Here, we conducted an analysis based on single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) on samples from the tumor core, paired non-tumorous tissue, and the leading-edge area obtained from 9 ICC patients to delineate the properties of cancer cells, immune microenvironment, and the intricate intercellular interactions within. The analysis results were further validated using H&E staining, multiple immunofluorescence staining (IHC), and a large transcriptome dataset.

Results

Tumor cells at the leading-edge area exhibit a heightened capacity for proliferation compared to those in the tumor core, often found in close proximity to the stroma, including endothelial cells and POSTN+ FAP+ fibroblasts. Within this region, CD8+ T cells are characterized by a naive phenotype, displaying low levels of cytotoxicity and exhaustion, a condition that may be linked to the impaired antigen-presenting capabilities of antigen-presenting cells (APCs). MAIT cells, which are the predominant CD8+ T cell subset infiltrating the leading-edge area of ICC, have been observed to recruit SPP1+ macrophages and are co-localized with POSTN+ cancer-associated fibroblasts (CAFs) in the stromal compartment. The presence of SPP1+ macrophages could potentially foster tumor progression through the activation of CD44 in tumor cells, as well as by their proangiogenic effects.

Conclusions

Utilizing scRNA-seq and spatial transcriptome technologies, our research delineates the distinct characteristics of ICC tumor cells within the leading-edge area, revealing how they interact with and influence the surrounding stroma to sculpt the immune microenvironment. These orchestrated interactions within the tumor milieu offer valuable insights and pinpoint potential therapeutic targets for intervention.

Legal entity responsible for the study

Peking University.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.