CD8陽性TRM細胞の肝細胞癌におけるマルチオミクス空間的特徴と免疫療法反応予測

Understanding CD8⁺ tissue-resident memory T cells (TRM) spatial characteristics in hepatocellular carcinoma (HCC) is challenging, and clarifying the spatial feature changes following immunotherapy represents an urgent research gap.

This study employs a multi-omics approach to analyze the spatial distribution and intercellular interactions of TRM cells in HCC tissues using radiomics, single-cell sequencing, and multiplex immunofluorescence histochemistry (m-IHC).

Our results show that the number of CD8⁺ TRM cells in HCC increases following immunotherapy. Furthermore, after dividing tumor tissues into the tumor core (TC), invasion margin (IM), and normal tissue (N), a increase in CD8⁺ TRM cells from the IM to the TC can be observed. Consistent with the results of single-cell sequencing analysis, this change in spatial characteristics may be associated with the interactions between CD8⁺ TRM cells and CD68⁺ cells.

Immunotherapy can modify the spatial characteristics of CD8⁺ TRM cells via regulating their crosstalk with other immune cells, and the spatial distribution of CD8⁺ TRM cells in the HCC tumor microenvironment (TME) correlates with immune checkpoint blockade (ICB) therapeutic efficacy. Clarifying the mechanisms of action of immunotherapeutic drugs and developing a non-invasive radiomics model to predict CD8⁺ TRM cell dynamics will facilitate the clinical management of HCC.