Prognostic values of tissue-resident CD8(+)T cells in human hepatocellular carcinoma and intrahepatic cholangiocarcinoma

BACKGROUND: Tissue-resident CD8(+)T cells (CD103(+)CD8(+)T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the proliferation and effector function of tissue-resident CD103(+)CD8(+)T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8(+)T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated. METHODS: In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8(+)T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell–cell communication between tumor-infiltrating CD103(+)CD8(+)T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data. RESULTS: Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8(+)T cells in human HCC and ICC. Elevated CD8(+)T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8(+)T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103(+)CD8(+)T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8(high)CD103(high) had a better OS, and the CD8(low)CD103(low) group tended to have a poorer prognosis in ICC. Evaluation of the CD103(+)CD8(+)T-cell ratio in CD8(+)T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103(+)CD8(+)T cells over total CD8(+)T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103(+)CD8(+)T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103(+)CD8(+)T cells over total CD8(+)T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103(+)CD8(+)T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion. CONCLUSION: The CD103(+) tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103(+)CD8(+)T cells might be helpful in assessing the on-treatment response of liver cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-023-03009-6.