연구실 오영식 학생(통합과정)이 진행한 연구가 Immune Network 에 2025년 12월 9일에 게재되었습니다.

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[제목] IL7-TBRII, a Dual Cytokine Modulator Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis

[논문 링크] https://immunenetwork.org/DOIx.php?id=10.4110/in.2025.25.e42

[Summary]

Tumor-infiltrating CD8+ T cells are a key determinant of anti-tumor efficacy in immunotherapy. IL-7 has been explored as a cytokine therapy to expand CD8+ T cells, showing promising anti-tumor effects in preclinical models. However, clinical outcomes remain limited, likely due to the immunosuppressive tumor microenvironment. To enhance the efficacy of IL-7 therapy, we reanalyzed publicly available single-cell RNA-sequencing (scRNA-seq) data of tumors treated with IL-7, identifying elevated TGF-β signaling in CD8+ T cells following treatment. As TGF-β impairs CD8+ T cell function and antagonizes IL-7 signaling, we developed a bifunctional fusion protein, recombinant human IL-7 (rhIL-7)-hyFc-sTBRII (IL7-TBRII), by fusing a TGF-β trap (Fc-TBRII) to rhIL-7-hyFc (IL7-Fc). We evaluated the binding affinities and functionalities of each domain in vitro and in vivo, and assessed anti-tumor effects in the MC38 colon cancer model. IL7-TBRII demonstrated superior anti-tumor efficacy compared to IL7-Fc or Fc-TBRII alone, primarily through increased infiltration of cytotoxic CD8+ T cells into tumors. Also, IL7-TBRII expanded the number of activated CD44+ CD8+ T cells. Furthermore, IL7-TBRII reduced metastasis in the 4T1 breast cancer model by reshaping the immune cell composition, and demonstrated synergistic efficacy when combined with radiotherapy or anti-CTLA-4 therapy in the EMT6 breast tumor model. These findings suggest that dual modulation of the IL-7 and TGF-β pathways by IL7-TBRII effectively reprograms the immune microenvironment in both primary and metastatic tumors, particularly by promoting CD8+ T cell activation and infiltration, thus offering a promising strategy to improve clinical responses to immunotherapy.