Tumor-Associated Macrophage Subsets: Shaping Polarization and Targeting

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7493 - 7493

Published: April 19, 2023

The tumor microenvironment (TME) is a critical regulator of growth, progression, and metastasis. Among the innate immune cells recruited to site, macrophages are most abundant cell population present at all stages progression. They undergo M1/M2 polarization in response signals derived from TME. M1 suppress while their M2 counterparts exert pro-tumoral effects by promoting angiogenesis, metastasis, resistance current therapies. Several subsets phenotype have been observed, often denoted as M2a, M2b, M2c, M2d. These induced different stimuli differ phenotypes well functions. In this review, we discuss key features each subset, implications cancers, highlight strategies that being developed harness TAMs for cancer treatment.

Language: Английский

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Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

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Immunotherapy in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7517 - 7517

Published: July 9, 2024

Breast cancer is a disease encompassing spectrum of molecular subtypes and clinical presentations, each with distinct prognostic implications treatment responses. has traditionally been considered an immunologically "cold" tumor, unresponsive to immunotherapy. However, trials in recent years have found immunotherapy be efficacious therapeutic option for select patients. categorized into different ranging from the most common positive hormone receptor (HR+), human epidermal growth factor 2 (HER2)-negative type, less frequent HER2- breast triple-negative (TNBC), highlighting necessity tailored strategies aimed at maximizing patient outcomes. Despite notable progress early detection new modalities, remains second leading cause death USA. Moreover, decades, incidence rates increasing, especially women younger than age 50. This prompted exploration approaches address this trend, offering prospects Immunotherapy class agents that revolutionized landscape many cancers, namely melanoma, lung cancer, gastroesophageal amongst others. Though belatedly, entered armamentarium approval pembrolizumab combination chemotherapy (TNBC) neoadjuvant advanced settings, thereby paving path further research integration immune checkpoint inhibitors other cancer. Trials exploring various therapies harness power symbiosis chemotherapeutic are ongoing hopes improving response prolonging survival Biomarkers precise selection utilization remain cardinal currently under investigation, some biomarkers showing promise, such as Program Death Lignat-1 (PDL-1) Combined Positive Score, Tumor Mutation Burden (TMB), Infiltrating Lymphocytes (TILs). review will present current immunotherapy, particularly inhibitors, types

Language: Английский

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A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Language: Английский

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CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies

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

Published: April 12, 2024

Surgery, chemotherapy, and endocrine therapy have improved the overall survival postoperative recurrence rates of Luminal A, B, HER2-positive breast cancers but treatment modalities for triple-negative cancer (TNBC) with poor prognosis remain limited. The effective application rapidly developing chimeric antigen receptor (CAR)-T cell in hematological tumors provides new ideas cancer. Choosing suitable specific targets is crucial applying CAR-T treatment. In this paper, we summarize therapy’s potential different subtypes based on existing research progress, especially TNBC. CAR-based immunotherapy has resulted advancements CAR-macrophages, CAR-NK cells, CAR-mesenchymal stem cells (MSCs) may be more safer treating solid tumors, such as However, tumor microenvironment (TME) side effects pose challenges to immunotherapy. cells-derived exosomes are advantageous therapy. Exosomes carrying CAR immense value provide a modality good effects. review, an overview development discuss progress CAR-expressing We elaborate TNBC prospects using CAR-MSCs

Language: Английский

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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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CAR-T therapy and targeted treatments: Emerging combination strategies in solid tumors

Med, Journal Year: 2024, Volume and Issue: 5(6), P. 530 - 549

Published: March 27, 2024

Language: Английский

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CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial

The Oncologist, Journal Year: 2024, Volume and Issue: 29(5), P. e622 - e634

Published: Jan. 4, 2024

Abstract Background The optimal treatment approach for hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2-negative MBC) with aggressive characteristics remains controversial, lack of randomized trials comparing cyclin-dependent kinase (CDK)4/6-inhibitors (CDK4/6i) + endocrine therapy (ET) chemotherapy ET. Materials and methods We conducted an open-label phase II trial (NCT03227328) to investigate whether ET is superior CDK4/6i HR+/HER2-negative MBC features. PAM50 intrinsic subtypes (IS), immunological features, gene expression were assessed on baseline samples. Results Among 49 patients (median follow-up: 35.2 months), median progression-free survival (mPFS) (11.2 months, 95% confidence interval [CI]: 7.7-15.4) was numerically shorter than mPFS (19.9 CI: 9.0-30.6) (hazard ratio: 1.41, 0.75-2.64). Basal-like tumors under exhibited worse PFS (mPFS: 11.4 3.00-not reached [NR]) overall (OS; mOS: 18.8 18.8-NR) compared other 20.7 9.00-33.4; NR, 24.4-NR). In the arm, luminal A showed poorer 5.1 2.7-NR) IS 13.2 10.6-28.1). Genes/pathways involved in BC cell proliferation associated outcomes, as opposite most immune-related genes/signatures, especially arm. CD24 only significantly both arms. Tertiary lymphoid structures higher tumor-infiltrating lymphocytes also favorable trends Conclusions KENDO trial, although closed prematurely, adds further evidence supporting use instead chemotherapy. IS, genomic, features are promising biomarkers personalize therapeutic choices.

Language: Английский

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Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer

Archivum Immunologiae et Therapiae Experimentalis, Journal Year: 2023, Volume and Issue: 71(1)

Published: Aug. 11, 2023

Language: Английский

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CAR-macrophage: Breaking new ground in cellular immunotherapy

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 3, 2024

Chimeric Antigen Receptor (CAR) technology has revolutionized cellular immunotherapy, particularly with the success of CAR-T cells in treating hematologic malignancies. However, have limited efficacy against solid tumors. To address these limitations, CAR-macrophages (CAR-Ms) leverage innate properties macrophages specificity and potency CAR technology, offering a novel promising approach to cancer immunotherapy. Preclinical studies shown that CAR-Ms can effectively target destroy tumor cells, even within challenging microenvironments, by exhibiting direct cytotoxicity enhancing recruitment activation other immune cells. Additionally, favorable safety profile their persistence tumors position as potentially safer more durable therapeutic options compared This review explores recent advancements including engineering strategies optimize anti-tumor preclinical evidence supporting use. We also discuss challenges future directions developing therapies, emphasizing potential revolutionize By harnessing unique macrophages, offer groundbreaking overcoming current limitations cell paving way for effective sustainable treatments.

Language: Английский

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