Single-cell RNA-Seq reveals the link between CD45 isoforms and tumor-infiltrating T cells heterogeneity in liver cancer

CD45 isoforms play a major role in characterizing T cell function, phenotype, and development. However, there is lacking comprehensive interrogation about the relationship between CD45 isoforms and T lymphocytes from cancer patients at the single-cell level yet. Here, we investigated the CD45 isoforms component of published 5,063 T cells of hepatocellular carcinoma (HCC), which has been assigned functional states. We found that the distribution of CD45 isoforms in T lymphocytes cells depended on tissue resource, cell type, and functional state. Further, we demonstrated that CD45RO and CD45RA dominate in characterizing the phenotype and function of T cell though multiple CD45 isoforms coexist in T cells, through a novel alternative splicing pattern analysis. We identified a novel development trajectory of tumor-infiltrating T cells from Tcm to Temra (effector memory T cells re-expresses CD45RA) after detecting two subpopulations in state of transition, Tcm (central memory T) and Tem (effector memory T). Temra, capable of high cytotoxic characteristics, was discovered to be associated with the stage of HCC and may be a target of immunotherapy. Our study presents a comprehension of the connection between CD45 isoforms and the function, states, sources of T lymphocytes cells in HCC patients at the single-cell level, providing novel insight for the effect of CD45 isoforms on T cell heterogeneity.