Advances in immunotherapy for triple-negative breast cancer

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Сен. 2, 2023

Immunotherapy has recently emerged as a treatment strategy which stimulates the human immune system to kill tumor cells. Tumor immunotherapy is based on editing, enhances antigenicity of cells and increases tumoricidal effect It also suppresses immunosuppressive molecules, activates or restores function, anti-tumor responses, inhibits growth f cell. This offers possibility reducing mortality in triple-negative breast cancer (TNBC).Immunotherapy approaches for TNBC have been diversified recent years, with breakthroughs this entity. Research checkpoint inhibitors (ICIs) made it possible identify different molecular subtypes formulate individualized schedules. review highlights unique microenvironment integrates analyzes advances ICI therapy. discusses strategies combination ICIs chemotherapy, radiation therapy, targeted emerging methods such nanotechnology, ribonucleic acid vaccines, gene Currently, numerous ongoing completed clinical trials are exploring utilization conjunction existing modalities TNBC. The objective these investigations assess effectiveness various combined determine most effective regimens patients TNBC.This provides insights into used overcome drug resistance immunotherapy, explores directions development

Язык: Английский

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Recent advances in targeted strategies for triple-negative breast cancer

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Авг. 28, 2023

Triple-negative breast cancer (TNBC), a highly aggressive subtype of cancer, negatively expresses estrogen receptor, progesterone and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is main form treatment for patients with TNBC, effectiveness TNBC still limited. The search more effective therapies urgent. Multiple targeted therapeutic strategies have emerged according to specific molecules signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, Notch poly ADP-ribose polymerase antibody-drug conjugates. Moreover, immune checkpoint example, pembrolizumab, atezolizumab, durvalumab, are widely explored clinic. We summarize recent advances therapy immunotherapy aim serving as reference development individualized future.

Язык: Английский

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Exploiting innate immunity for cancer immunotherapy

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Ноя. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Язык: Английский

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Targeting cytokine and chemokine signaling pathways for cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Язык: Английский

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Synergistic efficacy of simultaneous anti-TGF-β/VEGF bispecific antibody and PD-1 blockade in cancer therapy

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Авг. 12, 2023

Recently, therapeutic antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) have exerted potent anticancer effect in a variety of tumors. However, blocking the PD-1/PD-L1 axis alone is not sufficient to restore normal immune response. Other negative regulators antitumor immunity, like TGF-β VEGFA, are also involved escape tumor cells induce immunotherapy resistance.We developed novel anti-TGF-β/VEGF bispecific antibody Y332D based on Nano-YBODY™ technology platform. The CCK-8, flow cytometry, SBE4 luciferase reporter assay, western blotting transwell assays were used measure biological activities anti-TGF-β moiety. NFAT luminescent viability assay tube formation anti-VEGF vivo efficacy or combination with PD-1 blockade was evaluated H22, EMT-6, 4T1, AKT/Ras-driven murine hepatocellular carcinoma models. Immunofluorescent staining, RNA-seq quantitative RT-PCR adopted analyze alterations microenvironment.Y332D could maintain specific binding affinities for VEGFA. almost entirely counteracted vitro functions including immunosuppression, activated signaling, epithelial-mesenchymal transition (EMT), VEGF/VEGFR HUVEC proliferation formation. experiment data demonstrated that more effective inhibiting growth metastasis than monotherapies. In therapies, plus exhibited most durable effect. Mechanistically, upregulated density function tumor-infiltrating lymphocytes reinvigorated immunity.Y332D simultaneously block VEGF signalings. comparison monotherapies, combined exerts superior through improving microenvironment.

Язык: Английский

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Polysaccharides regulate Th1/Th2 balance: A new strategy for tumor immunotherapy

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 115976 - 115976

Опубликована: Дек. 3, 2023

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 are two key subsets of Th that exist relative equilibrium through the secretion cytokines suppress respective response. When type cytokine tumor microenvironment is altered, this may be disrupted, leading a shift from Th1/Th2 imbalance one decisive factors development malignant tumors. Therefore, focusing on balance responses enable future breakthroughs cancer immunotherapy. Polysaccharides can regulate between characteristic profiles, thereby improving microenvironment. To our knowledge, study most comprehensive assessment regulation by polysaccharides. Herein, we systematically summarized intrinsic molecular mechanisms polysaccharides provide new perspective potential target drugs for improved immunity delayed progression.

Язык: Английский

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T-cell infiltration and its regulatory mechanisms in cancers: insights at single-cell resolution

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Фев. 2, 2024

Abstract Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain can impair this response help escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand immunity improve therapeutic effect of cancer immunotherapy. The use single-cell RNA sequencing (scRNA-seq) allows high-resolution analysis precise composition with different phenotypes other microenvironmental factors, including non-immune stromal related molecules microenvironment various types. In review, we summarized research progress on crosstalk cytokines during using scRNA-seq provide insights into mechanisms regulating contribute new perspectives

Язык: Английский

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CAR-NK cells for cancer immunotherapy: recent advances and future directions

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Natural Killer (NK) cells, intrinsic to the innate immune system, are pivotal in combating cancer due their independent cytotoxic capabilities antitumor response. Unlike predominant treatments that target T cell immunity, limited success of immunotherapy emphasizes urgency for innovative approaches, with a spotlight on harnessing potential NK cells. Despite tumors adapting mechanisms evade cell-induced cytotoxicity, there is optimism surrounding Chimeric Antigen Receptor (CAR) This comprehensive review delves into foundational features and recent breakthroughs comprehending dynamics cells within tumor microenvironment. It critically evaluates applications challenges associated emerging CAR-NK therapeutic strategies, positioning them as promising tools evolving landscape precision medicine. As research progresses, unique attributes offer new avenue interventions, paving way more effective precise approach treatment.

Язык: Английский

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Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

Pharmaceuticals, Год журнала: 2024, Номер 17(4), С. 533 - 533

Опубликована: Апрель 20, 2024

The TGF-β family is a group of 25 kDa secretory cytokines, in mammals consisting three dimeric isoforms (TGF-βs 1, 2, and 3), each encoded on separate gene with unique regulatory elements. Each isoform plays unique, diverse, pivotal roles cell growth, survival, immune response, differentiation. However, many researchers the field often mistakenly assume uniform functionality among all isoforms. Although TGF-βs are essential for normal development cellular physiological processes, their dysregulated expression contributes significantly to various diseases. Notably, they drive conditions like fibrosis tumor metastasis/progression. To counter these pathologies, extensive efforts have been directed towards targeting TGF-βs, resulting range inhibitors. Despite some clinical success, agents yet reach full potential treatment cancers. A significant challenge rests effectively TGF-βs’ pathological functions while preserving roles. Many existing approaches collectively target isoforms, failing just specific deregulated ones. Additionally, most strategies tackle entire signaling pathway instead focusing disease-specific components or preferentially tumors. This review gives historical overview missed other reviews provides current landscape research, emphasizing isoform-specific disease implications. then delves into ongoing therapeutic cancer, stressing need more tools that disease-related components, advocating mechanism-based refined enhance effectiveness TGF-β-targeted cancer therapies.

Язык: Английский

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Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 6, 2024

Abstract The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold categorization based on the abundance of intra-tumoral immune cells. By incorporating spatial contexture, immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, mechanisms underlying these different phenotypes are yet to be comprehensively elucidated. In this review, we discuss how cells interact collectively shape landscape from perspectives cells, extracellular matrix, cancer metabolism, summarize potential therapeutic options according distinct immunophenotypes for personalized precision medicine.

Язык: Английский

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