The next frontier in immunotherapy: potential and challenges of CAR-macrophages

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Language: Английский

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Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies

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

Published: May 13, 2024

Breast cancer poses one of the largest threats to women’s health. Treatment continues improve for all subtypes breast cancer, but some subtypes, such as triple negative still present a significant treatment challenge. Additionally, metastasis and local recurrence are two prevalent problems in treatment. A newer type therapy, immunotherapy, may offer alternatives traditional treatments difficult-to-treat subtypes. Immunotherapy engages host’s immune system eradicate disease, with potential induce long-lasting, durable responses. However, systemic immunotherapy is only approved limited number indications, it benefits minority patients. Furthermore, related toxicities following administration potent immunomodulators limit dosing and, consequently, efficacy. To address these safety considerations efficacy, interest delivery at site tumor has increased. Numerous intratumorally delivered immunotherapeutics have been being explored clinically preclinically, including monoclonal antibodies, cellular therapies, viruses, nucleic acids, cytokines, innate agonists, bacteria. This review summarizes current past intratumoral clinical landscape well progress that made preclinical studies, focus on parameters considerations.

Language: Английский

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Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4832 - 4832

Published: April 29, 2024

This review offers a comprehensive exploration of the intricate immunological landscape breast cancer (BC), focusing on recent advances in diagnosis and prognosis through analysis circulating tumor cells (CTCs). Positioned within broader context BC research, it underscores pivotal role immune system shaping disease’s progression. The primary objective this investigation is to synthesize current knowledge aspects BC, with particular emphasis diagnostic prognostic potential offered by CTCs. adopts thorough examination relevant literature, incorporating breakthroughs field. methodology section succinctly outlines approach, specific focus CTC its implications for prognosis. Through review, insights into dynamic interplay between are highlighted, CTCs advancing methodologies refining assessments. Furthermore, presents substantiated results, contributing deeper understanding complexity BC. In conclusion, significance exploring profile patients, providing valuable novel utilization presentation findings emphasizes crucial dynamics, thereby opening avenues enhanced clinical management strategies.

Language: Английский

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Genomic Features of Homologous Recombination Deficiency in Breast Cancer: Impact on Testing and Immunotherapy

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 162 - 162

Published: Jan. 26, 2024

Genomic instability is one of the well-established hallmarks cancer. The homologous recombination repair (HRR) pathway plays a critical role in correcting double-stranded breaks (DSB) due to DNA damage human cells. Traditionally, BRCA1/2 genes HRR have been tested for their association with breast However, defects (HRD, also termed 'BRCAness'), which has up 50 genes, shown be involved tumorigenesis and treatment susceptibility poly-ADP ribose polymerase inhibitors (PARPis), platinum-based chemotherapy, immune checkpoint (ICIs). A reliable consensus on HRD scores yet established. Emerging evidence suggests that only subset cancer patients benefit from ICI-based immunotherapy. Currently, albeit limitations, expression programmed death-ligand 1 (PDL1) tumor mutational burden (TMB) are utilized as biomarkers predict favorable outcomes ICI therapy patients. Preclinical studies demonstrate an interplay between PDL1 expression. In this review, we outline current understanding genomic leading delineate various clinical trials. Furthermore, discuss potential strategies combining HRD-targeted immunotherapy achieve best healthcare

Language: Английский

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Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9302 - 9302

Published: Aug. 27, 2024

Insulin-like Growth Factor-1 (IGF-1) is a crucial mitogenic factor with important functions in the mammary gland, mainly through its interaction IGF-1 receptor (IGF-1R). This activates complex signaling network that promotes cell proliferation, epithelial to mesenchymal transition (EMT) and inhibits apoptosis. Despite extensive research, precise molecular pathways intracellular mechanisms activated by IGF-1, cancer, remain poorly understood. Recent evidence highlights essential roles of isoforms breast cancer (BC) development, progression, metastasis. The peptides define isoforms—IGF-1Ea, IGF-1Eb, IGF-1Ec—act as key points convergence for various influence growth, metastasis survival BC cells. aim this review provide detailed exami-nation role mature biology their potential use possible therapeutical targets.

Language: Английский

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Characteristics of the Immune Microenvironment and Progress in Immunotherapy for Triple-Negative Breast Cancer

World Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 15(01), P. 24 - 38

Published: Jan. 1, 2025

Language: Английский

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Unveiling the orchestration of T-cell dynamics: A comprehensive examination of their crucial role in revolutionizing immunotherapy for pancreatic and colon cancers

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 199 - 232

Published: Jan. 1, 2025

Language: Английский

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Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 25, 2025

Abstract This review discusses reprogramming the breast tumor immune microenvironment from an immunosuppressive cold state to immunologically active hot state. A complex interplay is revealed, in which accumulation of metabolic byproducts—such as lactate, reactive oxygen species (ROS), and ammonia—is shown impair T-cell function promote escape. It demonstrated that (TME) dominated by cytokines, including interleukin-10 (IL-10), transforming growth factorβ (TGFβ), IL-35. Notably, IL-35 produced regulatory T cells cancer cells. The conversion conventional into IL-35-producing induced cells, along with inhibition pro-inflammatory cytokine secretion, contributes suppression anti-tumor immunity. further key checkpoint molecules—such PD-1, PDL1, CTLA-4, TIM-3, LAG-3, TIGIT—are upregulated within TME, leading Tcell exhaustion diminished responses. blockade these checkpoints restore functionality proposed a strategy convert tumors ones robust effector cell infiltration. therapeutic potential chimeric antigen receptor (CAR)T therapy also explored, targeting specific tumor-associated antigens, such glycoproteins tyrosine kinases, highlighted. suggested CART efficacy can be enhanced combining inhibitors other immunomodulatory agents, thereby overcoming barriers imposed TME. Moreover, role microbiome regulating estrogen metabolism systemic inflammation reviewed. Alterations gut microbiota are affect microbiome-based interventions additional means facilitate cold-to-hot transition. concluded immunological pathways underpin suppression—through combination strategies involving blockade, therapies, modulation—the TME achieved. anticipated enhance infiltration function, improving overall immunotherapies better clinical outcomes for patients.

Language: Английский

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Integrating single‐cell transcriptomics and machine learning to predict breast cancer prognosis: A study based on natural killer cell‐related genes

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(15)

Published: Aug. 1, 2024

Abstract Breast cancer (BC) is the most commonly diagnosed in women globally. Natural killer (NK) cells play a vital role tumour immunosurveillance. This study aimed to establish prognostic model using NK cell‐related genes (NKRGs) by integrating single‐cell transcriptomic data with machine learning. We identified 44 significantly expressed NKRGs involved cytokine and T functions. Using 101 learning algorithms, Lasso + RSF showed highest predictive accuracy nine key NKRGs. explored cell‐to‐cell communication CellChat, assessed immune‐related pathways microenvironment gene set variation analysis ssGSEA, observed immune components HE staining. Additionally, drug activity predictions potential therapies, expression validation through immunohistochemistry RNA‐seq confirmed clinical applicability of The nomogram high concordance between predicted actual survival, linking higher purity risk scores reduced score. NKRG‐based offers novel approach for assessment personalized treatment BC, enhancing precision medicine.

Language: Английский

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Breast cancer immunotherapy: Realities and advances

Cancer Innovation, Journal Year: 2024, Volume and Issue: 3(5)

Published: Sept. 22, 2024

Breast cancer (BC) is the most common malignant tumor and main cause of death in women worldwide. With increased knowledge regarding escape mechanisms advances immunology, many new antitumor strategies such as nonspecific immunotherapies, monoclonal antibodies, anticancer vaccines, oncolytic viruses, among others, make immunotherapy a promising approach for treatment BC. However, these approaches still require meticulous assessment readjustment resistance modest response rates remain important barriers. In this article, we aim to summarize recent data available BC include results ongoing clinical trials approved therapies used monotherapies or combination with conventional treatments.

Language: Английский

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