Diverse approaches and sources to derive antitumor T cell for liver cancer: a single-cell sequence based research.

Abstract

Introduction: Despite advancements in adoptive cell therapy (ACT) for hematologic tumors, its role in solid tumors still lacks satisfactory performance, especially in Primary Liver Cancer (PLC). Therefore, further studies are needed on potential ACT sources for PLC.

Methods: Primary liver cancer patients who had not previously received treatment were prospectively enrolled in this research. Tumor tissues combined with lymph node and blood samples were acquired during surgery. Two different antigen-specific T-cell induction approaches were used to form cytotoxic T-cell groups from PBMCs, and antitumor T cells from tumor tissues combined with TDLNs were derived. A single-cell RNA sequence coupled with a T-cell receptor sequence was used to identify the cell subsets based on the molecular and functional properties of diverse antitumor T-cell induction approaches and sources.

Results: Three primary liver cancer patients were included in the present study. A total of 79,300 cell transcriptomes in 19 clusters were isolated from the clinical samples. After two different induction approaches, substantial amplification of immune cells occurred in both the CTL and CTL2 groups, with highly consistent T-cell subtypes, and selective amplification of antitumor T-cell clones in the two groups was also detected. The three-aspect comparison, which was based on the proliferation score, effect score and cytokine expression, indicated that the immunological effect of the mRNA approach was comparable to that of the multiantigen peptide approach. Finally, the antigen-specific expanded T-cell clones found in CTL, CTL2 and TAL-T cells indicated the potential of tumors combined with lymph nodes as sources for ACT.

Conclusions: Diverse antitumor T-cell induction approaches and sources were compared, revealing multiple effective options for antitumor T-cell derivation as a source of ACT for liver cancer.