ArticleBreast cancer research : BCR2023
Enhancement of PD-L1-attenuated CAR-T cell function through breast cancer-associated fibroblasts-derived IL-6 signaling via STAT3/AKT pathways.
Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 48 citations in OpenAlex.
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
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- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
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- Multi-omics exploration of hypoxia in gastric cancer.World journal of surgical oncology · 2026Article
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- Ellagic Acid Prevents Obesity in High-Fat Diet-Fed Rats by Ameliorating Oxidative Stress via Modulation of the PPARG/STAT3/p-AKT1 Axis.Foods (Basel, Switzerland) · 2026Article
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Dynamic feedback between IL-6 and TWIST1 drives pancreatic cancer progression.Translational gastroenterology and hepatology · 2026Article
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Dual Targeting of FAP-Directed Nanoparticles and FRα-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Stromal transcriptomics uncover LIF as a key effector in high tumor budding triple-negative breast cancer.Scientific reports · 2025Article
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- Cancer-associated fibroblasts promote tumor progression in fusion-positive rhabdomyosarcoma.Scientific reports · 2025Article
- Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy.Cytokine & growth factor reviews · 2025Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- Utility of Multicellular Spheroids for Investigating Mechanisms of Chemoresistance in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.Molecular cancer · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCarcinoma-associated fibroblasts (CAFs) play a critical role in cancer progression and immune cell modulation. In this study, it was aimed to evaluate the roles of CAFs-derived IL-6 in doxorubicin (Dox) resistance and PD-L1-mediated chimeric antigenic receptor (CAR)-T cell resistance in breast cancer (BCA).
methodsCAF conditioned-media (CM) were collected, and the IL-6 level was measured by ELISA. CAF-CM were treated in MDA-MB-231 and HCC70 TNBC cell lines and siIL-6 receptor (IL-6R) knocked down (KD) cells to determine the effect of CAF-derived IL-6 on Dox resistance by flow cytometry and on increased PD-L1 through STAT3, AKT and ERK1/2 pathways by Western blot analysis. After pre-treating with CM, the folate receptor alpha (FRα)-CAR T cell cytotoxicity was evaluated in 2D and 3D spheroid culture assays.
resultsThe results showed a significant level of IL-6 in CAF-CM compared to that of normal fibroblasts (NFs). The CM with high IL-6 level significantly induced Dox resistance; and PD-L1 expression through STAT3 and AKT pathways in MDA-MB-231 and HCC70 cells. These induction effects were attenuated in siIL-6R KD cells. Moreover, the TNBC cell lines that were CM-treated with STAT3 and an AKT inhibitor had a reduced effect of IL-6 on PD-L1 expression. BCA cells with high IL-6 containing-CM treatment had resistance to cancer cell killing by FRα CAR-T cells compared to untreated cells.
conclusionThese results highlight CAF-derived IL-6 in the resistance of chemotherapy and T cell therapy. Using inhibitors of IL6-STAT3/AKT-PD-L1 axis may provide a potential benefit of Dox and CAR-T cell therapies in BCA patients.
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