Tumor cell-derived EMP1 is essential for cancer-associated fibroblast infiltration in tumor microenvironment of triple-negative breast cancer DOI Creative Commons
Qi Wang, Dandan Li,

Haixiu Ma

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

Abstract The role of epithelial membrane protein 1 (EMP1) in tumor microenvironment (TME) remodeling has not yet been elucidated. In addition, the biological function EMP1 triple-negative breast cancer (TNBC) is largely unclear. this study, we examined infiltration landscape cell types TME cancer, and found that expression was positively correlated with stromal microenvironmental scores. Infiltration analysis immunohistochemical (IHC) staining serial sections confirmed critical cancer-associated fibroblast (CAF) infiltration. Cell co-culture assays, xenograft experiments, loss-of-function, gain-of-function, RNA sequencing studies, rescue assays were performed to confirm CAF vitro vivo. These findings revealed depletion TNBC cells resulted considerable inhibition vivo vitro. Mechanistically, knockdown induced a substantial decrease IL6 secretion from through NF-κB signaling pathway, hindering proliferation subsequently inhibiting progression metastasis. cumulative results indicate functions as an oncogene by mediating communication CAFs. Targeted suppressing promising strategy for treatment.

Language: Английский

Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers DOI Creative Commons
Yuanfang Li, Baiwei Zhao,

Juzheng Peng

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101042 - 101042

Published: Jan. 4, 2024

Drug resistance in cancer remains a major challenge oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as critical player development drug cells. This comprehensive review explores intricate relationship between NF-κB and cancer. We delve into molecular mechanisms through which activation contributes to against chemotherapeutic agents, targeted therapies, immunotherapies. Additionally, we discuss potential strategies overcome this by targeting signaling, such small molecule inhibitors combination therapies. Understanding multifaceted interactions is crucial for more effective strategies. By dissecting complex network NF-κB, hope shed light on novel therapeutic approaches that can enhance outcomes, ultimately improving prognosis patients. aims provide overview current state knowledge its role resistance, offering insights may guide future research interventions fight

Language: Английский

Citations

39
Targeting triple negative breast cancer stem cells using nanocarriers DOI Creative Commons
Nagasen Dasari, Girijasankar Guntuku, Sai Kiran S. S. Pindiprolu

et al.

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 7, 2024

Abstract Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, treatment responses. Categorization of based on the presence or absence estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2), leading to such as luminal A, B, HER2-positive, triple-negative breast (TNBC). TNBC, comprising around 20% all cancers, lacks expression ER, PR, HER2 receptors, rendering it unresponsive targeted therapies presenting significant challenges in treatment. TNBC associated with aggressive behavior, high rates recurrence, resistance chemotherapy. Tumor initiation, progression, are attributed stem cells (BCSCs), which possess self-renewal, differentiation, tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), immune modulation (cytokines, checkpoint inhibitors) among key targets discussed this review. However, targeting BCSC subpopulation presents challenges, including off-target effects, low solubility, bioavailability anti-BCSC agents. Nanoparticle-based offer promising approach target cellular processes implicated survival BSCS TNBC. In review, we explore nanocarrier-based approaches for BCSCs aiming overcome these improve outcomes patients. These nanoparticle-based therapeutic strategies hold promise addressing gap delivering while minimizing systemic toxicity enhancing efficacy. Graphical abstract

Language: Английский

Citations

20
Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota DOI Creative Commons
Min Yang, Jia Guo, Jinxian Li

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 7, 2025

Despite the approval of several artificial nanotherapeutics for treatment triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and high cost large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in therapy due to negligible systemic toxicity, bioavailability cost- effectiveness. this study, we developed an alternative strategy inhibit TNBC via Platycodon grandiflorum (PG)-derived (PGEVs). The PGEVs were isolated by ultracentrifugation sucrose gradient centrifugation method contained adequate functional components such as proteins, lipids, RNAs active molecules. exhibited remarkable stability, tolerating acidic digestion undergoing minimal changes simulated gastrointestinal fluid. They efficiently taken up tumor cells induced increased production reactive oxygen species (ROS), leading cell proliferation inhibition apoptosis, particularly line 4T1. Additionally, facilitated polarization tumor-associated macrophages (TAMs) toward M1 phenotype secretion pro-inflammatory cytokines. Further vivo investigations revealed that accumulated 4T1 tumors exerted effects through boosting anti-tumor immune responses modulating gut microbiota whether administered orally or intravenously (i.v.). conclusion, these findings highlight a natural, biocompatible efficient nanotherapeutic candidate treating TNBC.

Language: Английский

Citations

3
Inhibition of glycolysis-driven immunosuppression with a nano-assembly enhances response to immune checkpoint blockade therapy in triple negative breast cancer DOI Creative Commons

Xijiao Ren,

Zhuo Cheng,

Jinming He

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 2, 2023

Abstract Immune-checkpoint inhibitors (ICI) are promising modalities for treating triple negative breast cancer (TNBC). However, hyperglycolysis, a hallmark of TNBC cells, may drive tumor-intrinsic PD-L1 glycosylation and boost regulatory T cell function to impair ICI efficacy. Herein, we report tumor microenvironment-activatable nanoassembly based on self-assembled aptamer-polymer conjugates the targeted delivery glucose transporter 1 inhibitor BAY-876 (DNA-PAE@BAY-876), which remodels immunosuppressive TME enhance response. Poly β-amino ester (PAE)-modified CTLA-4-antagonizing aptamers (aptPD-L1 aptCTLA-4) synthesized co-assembled into supramolecular nanoassemblies carrying BAY-876. The acidic microenvironment causes PAE protonation triggers dissociation initiate aptamer release. selectively inhibits glycolysis deprive uridine diphosphate N-acetylglucosamine downregulate N-linked glycosylation, thus facilitating recognition aptPD-L1 anti-PD-L1 therapy. Meanwhile, treatment also elevates supply tumor-residing cells (Tregs) metabolically rewiring them an immunostimulatory state, cooperating with aptCTLA-4-mediated immune-checkpoint inhibition abolish Treg-mediated immunosuppression. DNA-PAE@BAY-876 effectively reprograms in preclinical models female mice provides distinct approach immunotherapy clinics.

Language: Английский

Citations

43
Epigenetic modulations in triple-negative breast cancer: Therapeutic implications for tumor microenvironment DOI Creative Commons
Linlin Zhou, Danny Yu

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107205 - 107205

Published: May 6, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptors, progesterone receptors and lacks HER2 overexpression. This absence of critical molecular targets poses significant challenges for conventional therapies. Immunotherapy, remarkably immune checkpoint blockade, offers promise TNBC treatment, but its efficacy remains limited. Epigenetic dysregulation, including altered DNA methylation, histone modifications, imbalances in regulators such as BET proteins, plays a crucial role development resistance to treatment. Hypermethylation tumor suppressor gene promoters the imbalance methyltransferases EZH2 deacetylases (HDACs) profoundly influence cell proliferation, survival, metastasis. In addition, epigenetic alterations critically shape microenvironment (TME), composition, cytokine signaling, expression, ultimately contributing evasion. Targeting these mechanisms with specific inhibitors HDAC combination immunotherapy represents compelling strategy remodel TME, potentially overcoming evasion enhancing therapeutic outcomes TNBC. review aims comprehensively elucidate current understanding modulation TNBC, on potential combining therapies overcome posed by this subtype.

Language: Английский

Citations

17
The immune checkpoint TIGIT/CD155 promotes the exhaustion of CD8 + T cells in TNBC through glucose metabolic reprogramming mediated by PI3K/AKT/mTOR signaling DOI Creative Commons
Mingyao Huang, Xiaoqin Yu, Qing Wang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 12, 2024

Abstract Objective The CD155/TIGIT axis has attracted considerable interest as an emerging immune checkpoint with potential applications in cancer immunotherapy. Our research focused on investigating the role of checkpoints progression triple-negative breast (TNBC). Methods We evaluated CD155 and TIGIT expression TNBC tissues using both immunohistochemistry (IHC) gene profiling. experiments, vivo vitro, provided evidence that inhibiting pathway reinstates ability CD8 + T cells to generate cytokines. To assess impact signaling blockade, we utilized Glucose Assay Kits Lactate measure alterations glucose lactate levels within cells. employed western blotting (WB) investigate glycolytic-related proteins PI3K/AKT/mTOR pathways following inhibition signaling. Results exhibits heightened a negative correlation extent infiltrating Furthermore, patients demonstrate elevated expression. findings indicate interaction between disrupts metabolism by suppressing activation pathway, ultimately leading reduced production cytokines Both vitro experiments have conclusively demonstrated capacity Moreover, administration blocking antibody against not only inhibits tumor growth but also augments functionality lymphocytes. Conclusions strongly suggest represents promising therapeutic target for treating TNBC.

Language: Английский

Citations

15
Implications of nanotherapeutic advancements to leverage multi-drug resistant breast cancer: The state-of-the-art review DOI Creative Commons

Adhithya Aravindan,

Ashutosh Gupta, Sudheer Moorkoth

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 106007 - 106007

Published: Aug. 5, 2024

Globally, cancer is regarded as a severe health issue. Among these breast (BC), the second most common kind in women after skin cancer. According to statistical data from NIH Cancer Institute, expected number of cases was around 3 lakh people, with 7.1 % fatality rate. The rise multidrug resistance (MDR) British Columbia issue it lowers effectiveness existing treatments. Traditional MDR treatment approaches BC have drawbacks, including toxicity, high cost, early discharge, restricted drug load before target, and poor effectiveness. Preventing has depended heavily on developing innovative therapy delivery methods utilizing nanomedicine new diagnosing treating BC. This review discusses its pathophysiology relation tumor kinetics. It focuses latest therapeutic over traditional like Surgery, Chemotherapy, Nanomedicine, Phototherapy, Immunotherapy, Gene therapy. also describes diagnostic techniques using MRI/PET, Mammography, Microwave Sensing, In-silico methods, Molecular techniques, AI-machine learning-based tools. discussed limitations nanoparticles article aims identify efficient ways diagnose treat prevent recurrence.

Language: Английский

Citations

13
Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer DOI Creative Commons

Sawsan Sudqi Said,

Wisam Nabeel Ibrahim

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 369 - 369

Published: Feb. 5, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in Therapeutic modalities, including checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, are explored preclinical clinical trials. Promising results emerge from combining ICIs anti-TGF-β VISTA, hindering TNBC growth. cells employ complex evasion strategies involving interactions stromal cells, suppressing recognition through various cytokines, chemokines, metabolites. The recent focus on unraveling humoral cellular components aims disrupt crosstalk within This review identifies latest mechanisms, exploring potential targets for trials overcome enhance patient survival rates.

Language: Английский

Citations

12
Autophagy in cancer immunotherapy: Perspective on immune evasion and cell death interactions DOI
Qiang Yu,

Jiajun Ding,

Shisen Li

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216856 - 216856

Published: April 5, 2024

Language: Английский

Citations

12
Toll-like receptors in breast cancer immunity and immunotherapy DOI Creative Commons

Joseph J. P. Zhou,

Lin Zhang,

Siyao Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 6, 2024

Toll-like receptors (TLRs) are a key family of pattern recognition (PRRs) in the innate immune system. The activation TLRs will not only prevent pathogen infection but also respond to damage-induced danger signaling. Increasing evidence suggests that play critical role breast cancer development and treatment. However, is double-edged sword can induce either pro-tumor activity or anti-tumor effect. underlying mechanisms these opposite effects TLR signaling fully understood. Targeting promising strategy for improving treatment, as monotherapies by other current therapies. Here we provide an update on immunity immunotherapy.

Language: Английский

Citations

11