Identification of MAGE-A10 specific T cell receptor promising in immunotherapy of hepatocellular carcinoma.

Due to the limitations of current treatment strategies, hepatocellular carcinoma (HCC) continues to impose a severe burden on people's health. In the process of exploring novel therapies, T cell receptor-engineered T cell (TCR-T) therapy has been extensively developed in HCC immunotherapy. Melanoma-associated antigen family A member 10 (MAGE-A10) is a cancer-testis antigen (CTA), specifically expressed on HCC cells. However, the identification of TCR-T targeting MAGE-A10 in HCC remains rarely discussed. In this study, single-cell RNA sequencing (scRNA-seq) and TCR sequencing (scTCR-seq) were performed on samples from HCC patients. The cellular landscape of HCC was illustrated through a single-cell atlas. Reactive T cells were defined based on the matched T cells. Additionally, most reactive T cells were enriched in CD4_CD69_Th, CD4_FOXP3_Treg, CD4_CXCL13_TEX, and CD8_CXCL13_TEX. GLIPH2 was utilized to cluster TCRs from reactive T cells, enabling the identification of reactive TCRs. TCRMatch predicted MAGE-A10 as a specific antigen recognized by one of the reactive TCRs. Furthermore, the affinity assessments between human leukocyte antigen (HLA), epitope of MAGE-A10, and the identified TCR were performed with NetMHCpan and DLpTCR. Finally, cytotoxicity assays indicated the specific recognition and killing of MAGE-A10-TCR-T cells against HCC cells, paving the way for TCR-T immunotherapy in HCC.