Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

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Natural killer cell homing and trafficking in tissues and tumors: from biology to application

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

Published: June 29, 2022

Abstract Natural killer (NK) cells, a subgroup of innate lymphoid act as the first line defense against cancer. Although some evidence shows that NK cells can develop in secondary tissues, mainly bone marrow (BM) and egress into blood circulation when they mature. They then migrate to settle down peripheral though special subsets home back BM or organs. Owing its success allogeneic adoptive transfer for cancer treatment “off-the-shelf” potential, cell-based immunotherapy is attracting increasing attention various cancers. However, insufficient infiltration adoptively transferred limits clinical utility, especially solid tumors. Expansion engineered chimeric antigen receptor (CAR) ex vivo prior by using cytokines alters profiles chemokine receptors, which affects tumor tissue. Several factors control cell trafficking homing, including cell-intrinsic (e.g., transcriptional factors), cell-extrinsic integrins, selectins, chemokines their corresponding signals induced cytokines, sphingosine-1-phosphate (S1P), etc.), cellular microenvironment. Here, we summarize mechanisms homing at steady state during development, aiming improve immunotherapy.

Language: Английский

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The emerging field of oncolytic virus-based cancer immunotherapy

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(2), P. 122 - 139

Published: Nov. 17, 2022

Language: Английский

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The Notch signaling pathway: a potential target for cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: May 2, 2023

Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated often affects networks controlling oncogenesis tumor progression. Meanwhile, modulate immune cells involved in anti- or pro-tumor responses immunogenicity. A comprehensive understanding these processes help with designing new drugs that target signaling, thereby enhancing effects cancer immunotherapy. Here, we provide an up-to-date overview how intrinsically regulates alterations stromal extrinsically regulate microenvironment (TME). We also discuss potential role immunity mediated gut microbiota. Finally, propose strategies for targeting These include oncolytic virotherapy combined inhibition nanoparticles (NPs) loaded regulators to specifically tumor-associated macrophages (TAMs) repolarize their functions remodel TME, combining specific efficient inhibitors activators checkpoint blockers (ICBs) synergistic anti-tumor therapy, implementing a customized effective synNotch circuit system enhance safety chimeric antigen receptor (CAR) cells. Collectively, this review aims summarize shapes improve

Language: Английский

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The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 15, 2024

Abstract Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about role of chemokines cytokines in these processes fueled renewed interest related research. These roles are frequently viewed as contentious due to their ability both suppress promote cancer progression. As a result, this review critically appraised existing literature discuss unique tumor microenvironment, well challenges future opportunities for exploiting develop novel targeted treatments. While modulatory molecules play an important suppression via enhanced cancer-cell identification by cytotoxic effector cells directly recruiting immunological stromal TME, we observed that they also proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, IL-21, entered clinical trials people with advanced cancer, while FDA has approved interferon-alpha IL-2. Nonetheless, low efficacy dose-limiting toxicity limit agents' full potential. Conversely, Chemokines tremendous potential increasing immune-cell penetration microenvironment promoting beneficial interactions. When combined activate lymphocytes, producing IL-2, CD80, all which strong anticancer effect. This phenomenon opens door development effective combination therapies, such therapies can reverse escape, chemotaxis immunosuppressive like Tregs, MDSCs, TAMs.

Language: Английский

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Therapeutic application of human type 2 innate lymphoid cells via induction of granzyme B-mediated tumor cell death

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 624 - 641.e23

Published: Jan. 10, 2024

Language: Английский

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Natural killer cells and type 1 innate lymphoid cells in cancer

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 66, P. 101709 - 101709

Published: Jan. 6, 2023

Language: Английский

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Advances in preclinical and clinical studies of oncolytic virus combination therapy

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 7, 2025

Oncolytic viruses represent a distinct class of that selectively infect and destroy tumor cells while sparing normal cells. Despite their potential, oncolytic encounter several challenges as standalone therapies. Consequently, the combination with other therapeutic modalities has emerged prominent research focus. This paper summarizes tumor-killing mechanisms viruses, explores integration radiotherapy, chemotherapy, immune checkpoint inhibitors, CAR-T, CAR-NK therapies, provides an overview related clinical trials. By synthesizing these advancements, this study seeks to offer valuable insights for translation virus

Language: Английский

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The cytokine network in acute myeloid leukemia

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

Published: Sept. 28, 2022

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy of the blood and bone marrow, characterized by clonal expansion stem progenitor cells rapid disease progression. Chemotherapy has been first-line treatment for AML more than 30 years. Application recent high-throughput next-generation sequencing technologies revealed significant molecular heterogeneity to AML, which in turn motivated efforts develop new, targeted therapies. However, due high complexity this disease, including multiple driver mutations coexistence competing tumorigenic clones, successful incorporation these new agents into clinical practice remains challenging. These continuing difficulties call identification innovative therapeutic approaches that are effective larger cohort patients. Recent studies suggest chronic immune stimulation aberrant cytokine signaling act as triggers initiation progression, facets might be exploited promising targets treatment. despite greater appreciation profiles exact functions cytokines pathogenesis not fully understood. Therefore, unravelling basis complex networks prerequisite alternatives based on targeting their receptors.

Language: Английский

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Tissue-specific transcriptional profiles and heterogeneity of natural killer cells and group 1 innate lymphoid cells

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(11), P. 100812 - 100812

Published: Nov. 1, 2022

Natural killer (NK) cells and type 1 innate lymphoid (ILC1s) are populations of non-T, non-B lymphocytes in peripheral tissues. Although NK ILC1 subsets have been described, their identification characteristics remain unclear. We performed single-cell RNA sequencing CITE-seq to explore heterogeneity between observed that although NK1 NK2 conserved spleen liver, ILC1s heterogeneous across identified sets genes expressed by related or characterizing unique each organ. The syndecan-4 appeared as a marker discriminating murine from organs. Finally, we revealed the expressions EOMES, GZMA, IRF8, JAK1, NKG7, PLEK, PRF1, ZEB2 define IL7R, LTB, RGS1 differentiate mice humans. Our data constitute an important resource improve our understanding NK-ILC1 origin, phenotype, biology.

Language: Английский

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