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

BackgroundTissue-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.MethodsIn 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.ResultsOur 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.ConclusionThe 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.

Automated summary

This study investigated tissue-resident CD8(+)T cells in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The expression levels of CD103 and CD8 in tumor tissues were correlated with tumor progression and prognosis, suggesting their potential as prognostic markers in liver cancer. Evaluation of tissue-resident CD103(+)CD8(+)T cells may also be useful for assessing treatment response.