| 研究実績の概要 |
Among exhausted T cells are precursor exhausted T cells (TPEX), a subset retaining proliferative capacity. While functionally distinct and crucial for antitumor immunity, TPEX shares some phenotypic traits with other T-cell subsets in tumor-infiltrating T-lymphocytes (TIL).
Here, we investigate TPEX-specific surface markers using chimeric antigen receptor (CAR)-engineered T cell-treated tumor models. Our findings reveal predominant CD83 expression in CCR7+PD1+ intratumoral CAR-T cells, compared to CCR7-PD1+ and CAR-negative T cells. CD83+CCR7+ CAR-T cells demonstrate enhanced antigen-induced proliferation and IL-2 production over CD83- T cells. Additionally, we confirm CD83 selective expression in CCR7+PD1+ T cells in primary TIL samples.
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| 今後の研究の推進方策 |
Since CD83 has been identified as a selective expression marker in CCR7+PD1+ T cells in primary TIL samples, it might be considered a prognostic marker for predicting clinical outcomes in ICB therapy. However, the specific ligand for CD83 has not yet been confirmed. Previous studies investigating the effect of CD83 ligation on conventional T cells have been controversial. While membranous CD83 expression in dendritic cells promotes T-cell expansion and effector functions, a soluble form of CD83 inhibits T cell proliferation. These apparently discrepant results may suggest that the optimal strength of CD83 exists for efficient T cell expansion. Our further study will focus on predicting ICB therapy outcomes based on CD83 expression and also aim to identify its ligands.
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