ArticleJournal for immunotherapy of cancer2020
Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 86 citations in OpenAlex.
- Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial.Journal for immunotherapy of cancer · 2025Trial
- Intratumoral TIGIT blockade augments antitumor responses and bypasses increased functionality of peripheral TIGIT+ NK cells in mouse and human models of bone and soft tissue sarcoma.Journal for immunotherapy of cancer · 2026Article
- Article
- KNTC1 and PRC1 define an immunosuppressive microenvironment and poor prognosis in liposarcoma.European journal of medical research · 2026Article
- Advances in IL-15-Based Cancer Immunotherapy and Divergent Immunological Effects of IL-2 and IL-15 Signaling via the Shared IL-2Rβγ Receptor.Frontiers in immunology · 2026Review
- Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.Frontiers in immunology · 2026Article
- Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review).Oncology letters · 2026Review
- HSP47 inhibition-induced CD155 expression through TRAF2 deubiquitination promotes tumor immune evasion.Journal for immunotherapy of cancer · 2025Article
- TIGIT antibody with PVR competitive ability enhances cancer immunotherapy and capable of eliciting anti-tumour immune memory.British journal of cancer · 2025Article
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials.Biomedicines · 2025Review
- Exploring the role of TIGIT in patients with Small Cell Lung Cancer as a novel predictor of prognosis and immunotherapy response.Cancer immunology, immunotherapy : CII · 2025Article
- Therapeutic effect of fully human anti-Nrp-1 antibody on non-small cell lung cancer in vivo and in vitro.Cancer immunology, immunotherapy : CII · 2025Article
- Emerging immunotherapies in osteosarcoma: from checkpoint blockade to cellular therapies.Frontiers in immunology · 2025Review
- Comparative transcriptomic analysis of tumor- infiltrating canine natural killer cells and candidate biomarkers from first-in-dog NK immunotherapy trials.Frontiers in immunology · 2025Article
- Target therapy of TIGIT; a novel approach of immunotherapy for the treatment of colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Bayesian Optimization-Enhanced Machine Learning for Osteosarcoma Risk Stratification Based on Sphingolipid Metabolism.Human mutation · 2025Article
- Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study.Frontiers in immunology · 2025Article
- Single cell atlas of canine natural killer cells identifies distinct circulating and tissue resident gene profiles.Frontiers in immunology · 2025Article
- Myokines May Be the Answer to the Beneficial Immunomodulation of Tailored Exercise-A Narrative Review.Biomolecules · 2024Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
purposeGiven the unmet need for novel immunotherapy in soft tissue sarcoma (STS), we sought to characterize the phenotype and function of intratumoral natural killer (NK) and T cells to identify novel strategies to augment tumor-infiltrating lymphocyte (TIL) function. EXPERIMENTAL
designUsing prospectively collected specimens from dogs and humans with sarcomas, archived specimens, and The Cancer Genome Atlas (TCGA) data, we evaluated blood and tumor NK and T cell phenotype and function and correlated those with outcome. We then assessed the effects of interleukin 15 (IL-15) stimulation on both NK and T cell activation and TIGIT upregulation. Finally, we evaluated cytotoxic effects of IL-15 combined with TIGIT blockade using a novel anti-TIGIT antibody.
resultsTILs were strongly associated with survival outcome in both archived tissue and TCGA, but higher TIL content was also associated with higher TIGIT expression. Compared with blood, intratumoral NK and T cells showed significantly higher expression of both activation and exhaustion markers, in particular TIGIT. Ex vivo stimulation of blood and tumor NK and T cells from patients with STS with IL-15 further increased both activation and exhaustion markers, including TIGIT. Dogs with metastatic osteosarcoma receiving inhaled IL-15 also exhibited upregulation of activation markers and TIGIT. Ex vivo, combined IL-15 and TIGIT blockade using STS blood and tumor specimens significantly increased cytotoxicity against STS targets.
conclusionIntratumoral NK and T cells are prognostic in STS, but their activation is marked by significant upregulation of TIGIT. Our data suggest that combined IL-15 and TIGIT blockade may be a promising clinical strategy in STS.
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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.