Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Language: Английский

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Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 18, 2022

Abstract Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients refractory or resistant to these therapies, mechanisms underlying tumor resistance have not been fully elucidated. Immunosuppressive such as myeloid-derived suppressive cells, tumor-associated macrophages, neutrophils, regulatory (Tregs), dendritic critical factors correlated with resistance. In addition, cytokines secreted by immunosuppressive also mediate progression escape Thus, targeting related signals is promising therapy improve efficacy immunotherapies reverse even certain success in preclinical studies specific types cancer, large perspectives unknown therapies undesirable outcomes clinical patients. this review, we comprehensively summarized phenotype, function, potential targets microenvironment.

Language: Английский

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Type I interferon-mediated tumor immunity and its role in immunotherapy

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: March 1, 2022

Immune checkpoint blockade (ICB) therapies have achieved remarkable clinical responses in patients with many different types of cancer; however, most who receive ICB monotherapy fail to achieve long-term responses, and some tumors become immunotherapy-resistant even hyperprogressive. Type I interferons (IFNs) been demonstrated inhibit tumor growth directly indirectly by acting upon immune cells, respectively. Furthermore, accumulating evidence indicates that endo- exogenously enhancing type IFNs a synergistic effect on anti-tumor immunity. Therefore, trials studying new treatment strategies combine IFN inducers are currently progress. Here, we review the cellular sources their roles regulation microenvironment. In addition, highlight immunotherapies based combination therapy between ICBs.

Language: Английский

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Targeting the tumor stroma for cancer therapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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STAT3 pathway in cancers: Past, present, and future

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: March 23, 2022

Abstract Signal transducer and activator of transcription 3 (STAT3), a member the STAT family, discovered in cytoplasm almost all types mammalian cells, plays significant role biological functions. The duration STAT3 activation normal tissues is transient event strictly regulated. However, cancer tissues, activated an aberrant manner induced by certain cytokines. continuous regulates expression downstream proteins associated with formation, progression, metastasis cancers. Thus, elucidating mechanisms regulation designing inhibitors targeting pathway are considered promising strategies for treatment. This review aims to introduce history, research advances, prospects concerning cancer. We consequent hallmarks tumor biology that pathway. Moreover, we summarize emerging development target novel drug delivery systems delivering these inhibitors. barriers against pathway, focus future on targets our perspective overall utility treatment also discussed.

Language: Английский

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Chronic inflammation, cancer development and immunotherapy

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune stromal etc.) and non-cellular to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), checkpoint factors other pro-inflammatory cytokines produced by TME are main mediators of intercellular communication TME, which link chronic stimulating different oncogenic signaling pathways improving escape promote In parallel, ability monocytes, T regulatory (Tregs) B (Bregs) perform homeostatic tolerogenic functions is hijacked leading local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy radiotherapy have improved last decades. However, clinical outcomes certain malignant cancers not satisfactory due drug resistance side effects. The application therapy (ICT) has brought hope treatment, although therapeutic efficacy still limited immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance disruption tumor-induced immunosuppression targeting suppressive well reactivation anti-tumor ICT. Here, we review impacts major their downstream molecules on We also discuss important management cancer.

Language: Английский

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Tumor-associated macrophages: an effective player of the tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up majority invading immune components, which are further categorized as anti-tumor M1 pro-tumor M2 subtypes. While known to have anti-cancer properties, recognized extend a protective role tumor. As result, manipulates TME in such way that it induces macrophage infiltration switching bias secure its survival. This M2-TAM promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, manipulation an immunosuppressive state. additionally promote emergence stem (CSCs), their ability originate, metastasize, relapse into tumors. CSCs also help revealing escape survival strategies during initiation phases. review describes reasons immunotherapy failure and, thereby, devises better impair tumor-TAM crosstalk. study will shed light on understudied TAM-mediated address much-needed holistic approach therapy, encompasses targeting cells, CSCs, all at same time.

Language: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Language: Английский

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