ArticleFrontiers in immunology2021
Targeting STAT3 Abrogates Tim-3 Upregulation of Adaptive Resistance to PD-1 Blockade on Regulatory T Cells of Melanoma.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Pooled it
- Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Distinct immunologic patterns of response and resistance to anti-PD-1/PD-L1-based immunotherapy in patients with soft tissue sarcoma.Frontiers in immunology · 2026Article
- Pan-cancer biomarkers of immune therapy resistance: mechanisms and clinical translation.Frontiers in cell and developmental biology · 2026Review
- The Role of Immune Checkpoint Inhibitors in Cancer Therapy: Mechanism and Therapeutic Advances.MedComm · 2025Review
- The concurrent silencing of Tim-3 and STAT-3 promotes tumor regression both in vitro and in ovo.BMC cancer · 2025Article
- Identification of anti-TIM-3 based checkpoint inhibitor combinations with activity in immunotherapy refractory melanoma models.Journal for immunotherapy of cancer · 2025Article
- Article
- Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Blocking secretion of exosomes by GW4869 dampens CD8Human cell · 2025Article
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Review
- Pharmacological strategies to overcome immune checkpoint inhibitor resistance in non-small cell lung cancer.Frontiers in oncology · 2025Review
- CD39Frontiers in oncology · 2025Review
- Prognostic value and immune infiltration of a tumor microenvironment-related PTPN6 in metastatic melanoma.Cancer cell international · 2024Article
- Noncoding Ribonucleic Acids (RNAs) May Improve Response to Immunotherapy in Pancreatic Cancer.ACS pharmacology & translational science · 2024Review
- rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.Journal for immunotherapy of cancer · 2024Article
- A Narrative Review of Current Knowledge on Cutaneous Melanoma.Clinics and practice · 2024Review
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Less than 20% of melanoma patients respond to programmed cell death-1 (PD-1) blockade immunotherapies. Thus, it is crucial to understand the dynamic changes in the tumor microenvironment (TME) after PD-1 blockade, for developing immunotherapy efficacy. Methods: A genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells, and B16-F10 melanoma mice were used as models. The cellular and molecular characteristics and mechanisms of Treg cells in melanoma were assessed by performing gene expression studies, immunohistochemistry, RNA sequencing, and flow cytometry. Results: Here, we evaluate the countenance of T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and various immunosuppressive factors within tumor-infiltrated Treg cells after treatment with anti-PD-1 or the indicator transduction and activator of transcription 3 (STAT3) inhibitors. Increased expression of Tim-3 is markedly observed within the tissues of the PD-1 blockade resistance of melanoma patients. Targeting STAT3 significantly boosts the response of resistant-PD-1 therapy within the melanoma mouse model. Mechanistically, the manifestation of STAT3 decreases the expression of Tim-3 and various cytokines in the purified Treg cells from individual PBMCs and the murine melanoma model, limiting the immunosuppression of Treg cells. Conclusions: Our findings indicate that Tim-3 expression on Treg cells within the TME is STAT3-dependent, providing support to STAT3 as a target and enhancing the immunotherapy for patients suffering from melanoma.
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Registered trials
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