ArticleJournal for immunotherapy of cancer2023
Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Synergy between TLR3-ligand and IFN-α in the transient sensitization of "Cold" tumors to PD-1 blockade and the induction of systemic immunity.Journal for immunotherapy of cancer · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy.Journal for immunotherapy of cancer · 2025Review
- IFNγ-mediated suppression of alternative NF-κB in tumor-resident myeloid cells promotes selective recruitment of cytotoxic but not regulatory T cells.Frontiers in immunology · 2025Article
- Meeting Highlights The 4th Marie Skłodowska-Curie Symposium on cancer research and care: Mechanisms of support for regional & international collaborations.Wiadomosci lekarskie (Warsaw, Poland : 1960) · 2025Article
- Mechanistic insights curcumin's anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interferenceFrontiers in cell and developmental biology · 2025Article
- Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer.Journal for immunotherapy of cancer · 2024Article
- Dendritic Cell Plasticity, Radiation, and Newton's Third Law.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Toll-like receptors in health and disease.MedComm · 2024Review
- Immunologic Factors Associated with Differential Response to Neoadjuvant Chemoimmunotherapy in Triple-Negative Breast Cancer.Journal of personalized medicine · 2024Article
- Review
- Targeting the tumor microenvironment to improve clinical outcomes in triple negative breast cancer patients and bridge the current disparity gap.Frontiers in immunology · 2024Article
- Bone marrow adipocytes and lung cancer bone metastasis: unraveling the role of adipokines in the tumor microenvironment.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPresence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs.
methodsSix evaluable patients (33-69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m
resultsPost-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8
conclusionsShort-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes.
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