IL7-TBRII - Original Article - Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis

Sep 30, 2026

Uploaded by Mary Man

Targeting tumor-infiltrating CD8+ T cells is central to immunotherapy, yet clinical benefit from IL-7 cytokine expansion is constrained by an immunosuppressive tumor microenvironment. Reanalysis of publicly available IL-7–treated tumors using scRNA-seq identifies elevated TGF-β signaling in CD8+ T cells. Since TGF-β disrupts CD8+ T cell function and counteracts IL-7, a dual cytokine modulator, IL7-TBRII, was engineered to fuse an IL-7 domain with a TGF-β trap. IL7-TBRII shows superior in vitro and in vivo anti-tumor activity, increased cytotoxic CD8+ infiltration, expanded activated CD44+ CD8+ T cells, reduced metastasis, and synergy with radiotherapy or anti-CTLA-4 therapy across mouse tumor models, supporting improved clinical responses.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

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Abstract

Introduction

Keywords

Immune Netw. 2025 Dec;25(6):e42 [https://doi.org/10.4110/in.2025.25.e42](https://doi.org/10.4110/in.2025.25.e42)[ ](https://doi.org/10.4110/in.2025.25.e42)pISSN 1598-2629·eISSN 2092-6685 Original Article IL7-TBRII, a Dual Cytokine Modulator Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis Youngsik Oh 1,†, Sora Kim 1,†, Ji-Hae Kim 1, Kun-Joo Lee 1, Dain Moon 1 , Chaerim Jeong 1, Hyun Gyung Kim 2, Seung-min Chun 1, Mi-Sun Byun 2, Seung-Woo Lee 1,* 1Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea 2Bio Research Institute, Genexine, Inc., Seoul 07789, Korea Received: Aug 28, 2025 Revised: Oct 10, 2025 ABSTRACT Accepted: Oct 14, 2025 Published online: Dec 9, 2025 Tumor-infiltrating CD8+ T cells are a key determinant of anti-tumor efficacy in *Correspondence to immunotherapy. IL-7 has been explored as a cytokine therapy to expand CD8+ T cells, Seung-Woo Lee showing promising anti-tumor effects in preclinical models. However, clinical outcomes Department of Life Sciences, Pohang remain limited, likely due to the immunosuppressive tumor microenvironment. To enhance University of Science and Technology, 77 the efficacy of IL-7 therapy, we reanalyzed publicly available single-cell RNA-sequencing CEeaoiln: gaswm_le-roe@, Npaom-gstec,.Poachkarng 37673, Korea. (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 †Youngsik Ohand Sora Kim contributed IL-7 signaling, we developed a bifunctional fusion protein, recombinant human IL-7 (rhIL-7) -equally to this work. hyFc-sTBRII (IL7-TBRII), by fusing a TGF-β trap (Fc-TBRII) to rhIL-7-hyFc (IL7-Fc) . Copyright © 2025. The Korean Association of We evaluated the binding affinities and functionalities of each domain in vitro and in vivo, Immunologists and assessed anti-tumor effects in the MC38 colon cancer model. IL7-TBRII demonstrated This is an Open Access article distributed superior anti-tumor efficacy compared to IL7-Fc or Fc-TBRII alone, primarily through under the terms of the Creative Commons increased infiltration of cytotoxic CD8+ T cells into tumors. Also, IL7-TBRII expanded the AttrcreaiiutveiocnoNmon-CmonsoomrgeircceniaslLesiebny-senc(h/4ttp0/s):// number of activated CD44+ CD8+ T cells. Furthermore, IL7-TBRII reduced metastasis in the which permits unrestricted non-commercial 4T1 breast cancer model by reshaping the immune cell composition, and demonstrated use, distribution, and reproduction in any synergistic efficacy when combined with radiotherapy or anti-CTLA-4 therapy in the medium, provided the original work is properly EMT6 breast tumor model. These findings suggest that dual modulation of the IL-7 and cited. TGF-β pathways by IL7-TBRII effectively reprograms the immune microenvironment in ORCID iDs both primary and metastatic tumors, particularly by promoting CD8+ T cell activation Youngsik Oh and infiltration, thus offering a promising strategy to improve clinical responses to [https://orcid.org/0009-0004-1776-6333](https://orcid.org/0009-0004-1776-6333) immunotherapy. Sora Kim [https://orcid.org/0000-0001-8438-8273](https://orcid.org/0000-0001-8438-8273) Keywords: Recombinant fusion proteins; Interleukin-7; Transforming growth factor beta; Ji-Hae Kim Immunotherapy [https://orcid.org/0000-0002-1388-5990](https://orcid.org/0000-0002-1388-5990)[ ](https://orcid.org/0000-0002-1388-5990)Kun-Joo Lee [https://orcid.org/0000-0001-5778-7535](https://orcid.org/0000-0001-5778-7535)[ ](https://orcid.org/0000-0001-5778-7535)Dain Moon [https://orcid.org/0000-0001-5244-3215](https://orcid.org/0000-0001-5244-3215) [https://immunenetwork.org](https://immunenetwork.org) 1/20 IL7-TBRII Inhibits Tumor Progression and Metastasis Chaerim Jeong [https://orcid.org/0009-0006-8863-3196](https://orcid.org/0009-0006-8863-3196)[ ](https://or

FAQs

Why was TGF-β targeted alongside IL-7 in this study?

Reanalysis of scRNA-seq data from IL-7–treated tumors showed elevated TGF-β signaling in CD8+ T cells. TGF-β was described as impairing CD8+ T cell function and antagonizing IL-7 signaling.

What is IL7-TBRII and how is it designed?

IL7-TBRII is a bifunctional fusion protein combining recombinant human IL-7 with a TGF-β trap (Fc-TBRII), so both pathways can be modulated together.

How did IL7-TBRII perform compared with IL7-Fc or Fc-TBRII alone?

IL7-TBRII demonstrated superior anti-tumor efficacy, increased infiltration of cytotoxic CD8+ T cells, expanded activated CD44+ CD8+ T cells, reduced metastasis, and improved outcomes especially when combined with radiotherapy or anti-CTLA-4 therapy.

Sep 30, 2026

Uploaded by Mary Man