ArticleJCI insight2020
Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Trifunctional antibody fusion proteins for targeted co-delivery of 4-1BBL with IL-15 or IL-21 to enhance antitumor immune responses.Frontiers in immunology · 2026Article
- Review
- IL-21 promotes the anti-tumor effect of anti-CD47 chimeric antigen receptor macrophages in ovarian cancer.Communications biology · 2025Article
- Interleukin 21-Armed EGFR-VHH-CAR-T Cell Therapy for the Treatment of Esophageal Squamous Cell Carcinoma.Biomedicines · 2025Article
- IL-21 Loading CaMnCOSmall (Weinheim an der Bergstrasse, Germany) · 2025Article
- Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21.Frontiers in immunology · 2025Article
- Inflammatory response signature score model for predicting immunotherapy response and pan-cancer prognosis.Computational and structural biotechnology journal · 2024Article
- Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.Bioactive materials · 2024Review
- Implications of glycosylation for the development of selected cytokines and their derivatives for medical use.Biotechnology advances · 2024Review
- Advancements and challenges in immunocytokines: A new arsenal against cancer.Acta pharmaceutica Sinica. B · 2024Review
- Stimulating the Antitumor Immune Response Using Immunocytokines: A Preclinical and Clinical Overview.Pharmaceutics · 2024Review
- Immunometabolism of CD8Trends in cancer · 2024Review
- Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.Cancer immunology, immunotherapy : CII · 2024Article
- Germinal center cytokine driven epigenetic control of Epstein-Barr virus latency gene expression.PLoS pathogens · 2024Article
- IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials.Immune network · 2024Review
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Myeloid-Derived Suppressor Cells Induce Exhaustion-Like CD8International journal of biological sciences · 2024Article
- CD8Immunity · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lack of sufficient functional tumor-infiltrating lymphocytes in the tumor microenvironment (TME) is one of the primary indications for the poor prognosis of patients with cancer. In this study, we developed an Erbitux-based IL-21 tumor-targeting fusion protein (Erb-IL21) to prolong the half-life and improve the antitumor efficacy of IL-21. Compared with Erb-IL2, Erb-IL21 demonstrated much lower toxicity in vivo. Mechanistically, Erb-IL21 selectively expanded functional cytotoxic T lymphocytes but not dysfunctional CD8+ T cells in the TME. We observed that the IL-21-mediated antitumor effect largely depended on the existing intratumoral CD8+ T cells, instead of newly migrated CD8+ T cells. Furthermore, Erb-IL21 overcame checkpoint blockade resistance in mice with advanced tumors. Our study reveals that Erb-IL21 can target IL-21 to tumors and maximize the antitumor potential of checkpoint blockade by expending a subset of tumor antigen-specific CD8+ T cells to achieve effective tumor control.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.