Long-acting IL-7 induces distinct transcriptomic features in peripheral T cells of patients with solid tumors
Hocheol Jang, Jeong Yeon Kim, Sojeong Kim, Heewon Kim, Mi Sun Byun, Myung Ah Lee, Jong Hee Chang, Do-Hyun Nam, Tae Won Kim, Sin-Soo Jeun, Joo Hyuk Sohn, Su-Hyung Park, Eui-Cheol Shin
Hocheol Jang, Jeong Yeon Kim, Sojeong Kim, Heewon Kim, Mi Sun Byun, Myung Ah Lee, Jong Hee Chang, Do-Hyun Nam, Tae Won Kim, Sin-Soo Jeun, Joo Hyuk Sohn, Su-Hyung Park, Eui-Cheol Shin
View: Text | PDF
Clinical Research and Public Health Clinical Research Immunology Oncology

Long-acting IL-7 induces distinct transcriptomic features in peripheral T cells of patients with solid tumors

Abstract

BACKGROUND IL-7 is a critical cytokine in T cell development, survival, and homeostasis. Previous preclinical and clinical studies reported that IL-7 treatment increased T cell counts, but its effect on peripheral blood T cells in cancer patients and molecular mechanisms have not been explored.METHODS We investigated effects of long-acting recombinant human IL-7 conjugated to a hybrid IgD/IgG4 Fc domain (rhIL-7-hyFc) on peripheral T cells in patients with advanced solid tumors. Peripheral blood samples were collected before and after treatment, followed by analysis through single-cell transcriptomics and flow cytometry.RESULTS We found that rhIL-7-hyFc induced marked expansion of proliferating T cells, and promoted transcriptional changes associated with immune activation, cell cycle progression, and antiapoptosis. Trajectory analysis revealed that posttreatment T cells had distinct transcriptional states enriched for cytokine- and TCR-mediated signaling pathways. Notably, a second dose administered after 3 weeks yielded diminished proliferation and minimal transcriptional changes, which were independent of antidrug antibody or CD127 downmodulation. Examination of elements of the IL-7 signaling pathway revealed intact proximal signaling (e.g., STAT5 phosphorylation) but downregulation of distal elements, including PIM-1 kinase and c-Myc.CONCLUSIONS Our results demonstrate that rhIL-7-hyFc induces robust peripheral T cell expansion and activation in patients with solid tumors, supporting its potential use for lymphopenic patients treated with cancer immunotherapy.TRIAL REGISTRATION ClinicalTrials.gov NCT03478995 and NCT03619239.FUNDING National Research Foundation of Korea (NRF-2022R1A2C3007292 and RS-2024-00439160), Ministry of Food and Drug Safety (RS-2025-02213409), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (RS-2025-25460003).

Authors

Hocheol Jang, Jeong Yeon Kim, Sojeong Kim, Heewon Kim, Mi Sun Byun, Myung Ah Lee, Jong Hee Chang, Do-Hyun Nam, Tae Won Kim, Sin-Soo Jeun, Joo Hyuk Sohn, Su-Hyung Park, Eui-Cheol Shin

×

Figure 2

rhIL-7-hyFc–induced transcriptional changes in T cells.

Options: View larger image (or click on image) Download as PowerPoint
rhIL-7-hyFc–induced transcriptional changes in T cells. (A) Row-normaliz...
(A) Row-normalized heatmap of differentially expressed genes (DEGs) between W0 and W1. Representative genes are annotated. (B) Pathway enrichment analysis of DEGs. Pathways enriched at baseline (blue) and after rhIL-7-hyFc treatment (red) are shown. (C) GSEA of upregulated pathways after rhIL-7-hyFc treatment, among CD8+ and CD4+ T cells. (D) Module scores for the GO term “Regulation of T cell apoptotic process” were calculated and compared between W0 and W1. Unpaired t test was used for P value calculation. (E and F) Mean BCL2 expression per sample among CD8+ T cells and CD4+ T cells from scRNA-seq data (E) (n = 7) and from geometric mean fluorescence intensity (gMFI) measured by flow cytometry (F) (n = 12). (G) Flow cytometry–measured CD38 gMFI among CD8+ and CD4+ T cells, subdivided into total, naive, central memory, effector memory, and EMRA subsets (n = 9). Statistical testing was conducted using the paired Wilcoxon test (E–G). *P < 0.05, **P < 0.01, ***P < 0.001.