Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Journal of Cancer, Journal Year: 2023, Volume and Issue: 14(5), P. 850 - 873

Published: Jan. 1, 2023

Programmed death-1 is a protein found on the surface of immune cells that can interact with its ligand, programmed death-ligand 1 (PD-L1), which expressed plasma membrane, secreted cellular exosomes, in cell nuclei, or as circulating soluble protein. This interaction lead to escape cancer patients. In clinical settings, PD-L1 plays an important role tumor disease diagnosis, determining therapeutic effectiveness, and predicting patient prognosis. inhibitors are also essential components immunotherapy. Thus, detection levels crucial, especially era precision therapy. recent years, innovations have been made traditional immunoassay methods development new immunoassays for detection. review aims summarize research progress technology highlight applications PD-L1.

Language: Английский

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Cancer cell‐derived exosomal miR‐20a‐5p inhibits CD8⁺ T‐cell function and confers anti‐programmed cell death 1 therapy resistance in triple‐negative breast cancer

Cancer Science, Journal Year: 2023, Volume and Issue: 115(2), P. 347 - 356

Published: Dec. 21, 2023

Abstract Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects malignant progression and therapy resistance of triple‐negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T‐cell function, especially antibodies against programmed cell death 1 (PD‐1) or its ligand PD‐L1, are emerging as new promising for TNBC patients. However, only very limited patients showed complete partial response to anti‐PD‐1 treatment. Dysfunction CD8 + T cells is one key reasons escape TNBC. The regulation exosome‐derived cirmiRNAs on deserves more investigation. Here, cirmiR‐20a‐5p level was significantly upregulated plasma culture supernatant cells. High abundance correlated with a worse prognosis secreted form exosomes by Exosomal internalized resulted dysfunction T. A mechanism study uncovered targeted nuclear protein ataxia‐telangiectasia (NPAT) decreased NPAT expression An vivo xenograft mouse model conferred treatment resistance. Collectively, these findings indicated released via exosome promotes growth leads immunosuppression inducing dysfunction. This suggests targeting might novel strategy overcoming immunotherapy.

Language: Английский

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Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review

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

Published: Dec. 13, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the absence progesterone and estrogen receptors low (or absent) HER2 expression. TNBC accounts for 15-20% all cancers. It associated with younger age, a higher mutational burden, increased risk recurrence mortality. Standard treatment primarily relies on cytotoxic agents, such as taxanes, anthracyclines, platinum compounds both early advanced stages disease. Several targeted therapies, including bevacizumab sunitinib, have failed to demonstrate significant clinical benefit in TNBC. The emergence immune checkpoint inhibitors (ICI) has revolutionized treatment. By stimulating system, ICIs induce durable anti-tumor response across various solid tumors. particularly promising target due levels tumor-infiltrating lymphocytes (TIL), PD-L1 expression, which generates tumor-specific neoantigens that activate cells. administered monotherapy yields only modest response; however, rates significantly improve when are combined tumors expressing PD-L1. Pembrolizumab approved use combination standard chemotherapy. However, more research needed identify potent biomarkers, better elucidate synergism other agents. In this review, we explore challenges immunotherapy TNBC, examining mechanisms tumor progression mediated cells within microenvironment, signaling pathways involved primary acquired resistance. Finally, provide comprehensive overview ongoing trials underway investigate novel immune-targeted therapies

Language: Английский

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Guardians and Mediators of Metastasis: Exploring T Lymphocytes, Myeloid-Derived Suppressor Cells, and Tumor-Associated Macrophages in the Breast Cancer Microenvironment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6224 - 6224

Published: June 5, 2024

Breast cancers (BCs) are solid tumors composed of heterogeneous tissues consisting cancer cells and an ever-changing tumor microenvironment (TME). The TME includes, among other non-cancer cell types, immune influencing the context tissues. In particular, cross talk their interactions with dramatically influence BC dissemination, immunoediting, outcomes therapies. Tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), myeloid-derived suppressor (MDSCs) represent prominent populations breast TMEs, they have important roles in immunoescape dissemination. Therefore, this article we review features TILs, TAMs, MDSCs BCs. Moreover, highlight mechanisms by which these remodel lead to metastasis.

Language: Английский

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Tumor Cell-Associated IL-1α Affects Breast Cancer Progression and Metastasis in Mice through Manipulation of the Tumor Immune Microenvironment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3950 - 3950

Published: April 2, 2024

IL-1α is a dual function cytokine that affects inflammatory and immune responses plays pivotal role in cancer. The effects of intracellular on the development triple negative breast cancer (TNBC) mice were assessed using CRISPR/Cas9 system to suppress expression 4T1 cells. Knockout cells modified multiple genes, including downregulation cytokines chemokines involved recruitment tumor-associated pro-inflammatory Orthotopical injection knockout (KO) into BALB/c led significant decrease local tumor growth lung metastases, compared wild-type (4T1/WT) Neutrophils myeloid-derived suppressor abundant tumors developing after 4T1/WT cells, whereas more antigen-presenting observed microenvironment KO This switch correlated with increased infiltration CD3+CD8+ NKp46+cells. Engraftment immunodeficient NOD.SCID resulted rapid growth, metastasis comparison engraftment Our results suggest TNBC progression by modulating interplay between immunosuppressive vs. cytotoxic

Language: Английский

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Synergistic effect of human uterine cervical mesenchymal stem cell secretome and paclitaxel on triple negative breast cancer

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 25, 2024

Abstract Background Triple-negative breast cancer (TNBC) is the most lethal subtype of and, despite its adverse effects, chemotherapy standard systemic treatment option for TNBC. Since, it utmost importance to consider combination different agents achieve greater efficacy and curability potential, MSC secretome a possible innovative alternative. Methods In present study, we proposed investigate anti-tumor effect chemical agent (paclitaxel) with complex biological product, derived from human Uterine Cervical Stem cells (CM-hUCESC) in Results The paclitaxel CM-hUCESC decreased cell proliferation invasiveness tumor induced apoptosis vitro (MDA-MB-231 and/or primary cells). was confirmed mouse xenograft model showing that both products has significant reducing growth. Also, pre-conditioning hUCESC sub-lethal dose enhances reduced significantly growth even allows diminish vivo. This part due action extracellular vesicles (EVs) soluble factors, such as TIMP-1 − 2. Conclusions conclusion, our data demonstrate synergistic on TNBC opens an opportunity reduce chemotherapeutic agents, which may decrease chemotherapy-related toxicity.

Language: Английский

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Specific microbiome patterns and their association with breast cancer: the intestinal microbiota as a potential biomarker and therapeutic strategy

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Abstract Breast cancer (BC) is one of the most diagnosed cancers in women. Based on histological characteristics, they are classified as non-invasive, or situ (tumors located within milk ducts lobules) and invasive. BC may develop from carcinomas over time. Determining prognosis predicting response to treatment essential tools manage this disease reduce its incidence mortality, well promote personalized therapy for patients. However, half cases not associated with known risk factors. In addition, some patients resistance relapse. Therefore, it necessary identify new biomarkers strategies that improve existing therapies. regard, role microbiome being researched could play a carcinogenesis efficacy This review aims describe specific patterns BC. For this, literature search was carried out PubMed database using MeSH terms “Breast Neoplasms” “Gastrointestinal Microbiome”, including 29 publications. Most studies have focused characterizing gut breast tissue Likewise, animal models vitro investigated impact microbiota (GM) treatments effects tumor cells were included. results included articles, be an imbalance GM. varied depending molecular type, stage grade cancer, menopause, menarche, body mass index, physical activity. microbial profile identified biomarker. On other hand, suggest GM influence microorganisms bacterial metabolites therapies development.

Language: Английский

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Nucleic acid vaccines‐based therapy for triple‐negative breast cancer: A new paradigm in tumor immunotherapy arena

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(3)

Published: March 29, 2024

Nucleic acid vaccines (NAVs) have the potential to be economical, safe, and efficacious. Furthermore, just chosen antigen in pathogen is target of immune responses brought on by NAVs. Triple-negative breast cancer (TNBC) treatment shows great promise for nucleic acid-based vaccines, such as DNA (as plasmids) RNA messenger [mRNA]). Moreover, offer a compelling approach that can elicit targeted long-lasting against tumor antigens. Bacterial plasmids encode antigens immunostimulatory molecules serve foundation vaccines. In 1990s, plasmid encoding influenza A nucleoprotein triggered protective cytotoxic T lymphocyte (CTL) response, marking first instance vaccine-mediated immunity. Similarly, vitro transcribed mRNA was successfully used animals 1990. At point, mice were given an injection gene sequence, researchers saw production protein. We begin this review summarizing our existing knowledge Next, we addressed NAV delivery, emphasizing need increase efficacy TNBC.

Language: Английский

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Present and Future of Immunotherapy for Triple-Negative Breast Cancer

Cancers, Journal Year: 2024, Volume and Issue: 16(19), P. 3250 - 3250

Published: Sept. 24, 2024

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), human epidermal growth factor receptor 2 (HER2), and progesterone (PRs). TNBC has poorest prognosis among subtypes is more likely to respond immunotherapy due its higher PD-L1 a greater percentage tumor-infiltrating lymphocytes. Immunotherapy revolutionized treatment, especially with FDA’s approval pembrolizumab (Keytruda) combined chemotherapy for advanced cases, opening new avenues treating this deadly disease. Although can significantly improve patient outcomes in subset patients, achieving desired response rate all remains an unmet clinical goal. Strategies that enhance responses immune checkpoint blockade, including combining chemotherapy, molecularly targeted therapy, or radiotherapy, may rates outcomes. In review, we provide short background on explore different types strategies are currently being evaluated TNBC. Additionally, review why combination be beneficial, overview strategies, discuss novel immunotherapeutic opportunities approved near future

Language: Английский

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Inhibition of EMT driver PTK6 enhances anti-tumor immune responses against triple-negative breast cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

ABSTRACT The non-receptor tyrosine kinase PTK6 is expressed in 70% of triple negative breast cancers (TNBC) and an oncogenic driver epithelial-mesenchymal transition (EMT). EMT promotes metastasis immune evasion TNBC. Therefore, targeting drivers could reverse these properties lead to more favorable outcomes. Treatment TNBC tumors with a small molecule inhibitor (P21d) suppressed their growth vivo . Tumor inhibition by P21d dependent on induced response because: 1) observed immunocompetent, but not immunodeficient, mice; 2) increases tumor-infiltrating CD8 + T NK cells decreases immunosuppressive myeloid-derived suppressor cells; 3) tumor abrogated co-treatment or cell-depleting antibodies. These effects cytotoxic TILs are phenocopied the knockdown tumoral SNAIL, which supports as mechanism for enhanced anti-tumor response. RNA sequencing (RNA-seq) profiling P21d-treated also revealed changes consistent activation identified CXCL10 critical chemokine intratumorally that recruitment NK/CD8+ site, leading inhibition. Our study highlights novel microenvironmental functions important consequences new immunotherapeutic approaches

Language: Английский

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