(A) single-cell transcriptome analysis of the effects of exogenous interleukin-7 on peripheral blood T cells in patients with malignancy

Abstract

IL-7 is a cytokine known to play a key role in the survival, proliferation and differentiation of peripheral blood T cells. This makes it an attractive candidate for therapeutic applications, particularly in conditions characterized by immunocompromised individuals. IL-7 has been used in clinical trials for various conditions associated with lymphopenia, but the exact mechanisms of its effects on peripheral blood T cells have remained unclear. Single-cell transcriptome analysis allows the analysis of individual cells, allowing the identification of transcriptomic heterogeneity and the specific effects of IL-7 at the single cell level in cancer patients. Cancer patients received a single dose of recombinant IL-7 and their peripheral blood T cells were analyzed one week and three weeks after injection. One week after recombinant IL-7 injection, peripheral blood T cells showed decreased expression of genes and transcription factors that maintain cellular quiescence. Most cells showed an increase in cellular activity. In addition, the proportion of proliferating T cells in the total number of T cells increased. However, when recombinant IL-7 was administered 3 weeks later, the effects observed after one week appeared to diminish, suggesting possible desensitization or some other mechanism of adaptation. A decrease in signaling downstream of STAT5 and reduced expression of the transcription factor c-Myc, which is critical for cell proliferation, were observed. The reduced response to IL-7 observed three weeks after injection may be due to changes in the gene expression profile of peripheral blood T cells. Single-cell RNA sequencing shows that the transcriptomic landscape was different before and 3 weeks after IL-7 treatment. This study provides an in-depth analysis of the IL-7 response in human T cells and suggests the mechanism of the decreased response with repeated use of IL-7. Future studies may need to explore ways to improve the efficacy of IL-7 through repeated use.