Single-cell analysis reveals XCL1+ CD8+ T cells as a therapeutic target in hepatocellular carcinoma

XCL1 (lymphotactin), a C-chemokine primarily produced by activated CD8+ T cells, remains poorly characterized in the context of immunotherapy. Here, we conducted comprehensive analyses based on multiple scRNA-seq datasets to identify the presence of XCL1+ CD8+ T cells in hepatocellular carcinoma (HCC) tumor microenvironment. Multiplex Immunohistochemistry and clinical data revealed that the infiltration of this cell population correlated with favorable outcomes. Cell-cell communication demonstrated interactions between XCL1+ CD8+ T cells and NK cells or myeloid cells via CD99 and MIF signaling pathways, respectively. These findings were further supported by spatial transcriptomic data. Using two independent bulk RNA-seq datasets, we found the mean of expression of XCL1 and CD8A could be an independent factor for prognosis of HCC, and next built a prediction score with five marker genes involved in XCL1+ CD8+ T cell population. Our findings proposed that XCL1 may play a key role in anti-tumor immunity and XCL1+ CD8+ T cell population could be a potential target to improve responses for immunotherapy in HCC.