Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(6)

Published: May 2, 2024

Abstract Senescent cells have a profound impact on the surrounding microenvironment through secretion of numerous bioactive molecules and inflammatory factors. The induction therapy-induced senescence by anticancer drugs is known, but how senescent tumor influence immune landscape, particularly neutrophil activity, still unclear. In this study, we investigate cellular in breast cancer subsequent immunomodulatory effects neutrophils using CDK4/6 inhibitor palbociclib, which approved for treatment under intense investigation additional malignancies. Our research demonstrates that palbociclib induces reversible form endowed with an secretome capable recruiting activating neutrophils, part action interleukin-8 acute-phase serum amyloid A1. activation accompanied release extracellular trap phagocytic removal cells. These findings may be relevant success therapy as neutrophil-driven inflammation can differently affect progression. results reveal already demonstrated macrophages natural killer cells, recruited engaged to participate their clearance. Understanding interplay between lead innovative strategies cope chronic or tumor-associated inflammation.

Language: Английский

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Neutrophil Extracellular Traps: Potential Thrombotic Markers and Therapeutic Targets in Colorectal Cancer

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Neutrophil extracellular traps (NETs) are promising promoters in venous thromboembolism (VTE). In the present study, we have investigated potential thrombogenic role of NETs colorectal cancer (CRC). A total 583 patients with gastrointestinal malignancies who were diagnosed or without VTE by extremities arteriovenous ultrasound and computed tomography enrolled. The incidence CRC was as high 17.53%. serological ELISA experiments, Cit-H3, MPO cfDNA significantly overexpressed compared to healthy individuals. Neutrophils from produced appreciable amounts after stimulation phorbol-12-myristate-13-acetate, which lacking CfDNA positively correlated plasmin-α2-antiplasmin complex tissue plasmin activator inhibitor-1 complex, Cit-H3 suggesting that associated increased fibrinolytic activity. We screened some NETs-related genes analysing several high-throughput sequencing datasets NETs. FCGR1A identified optimal target gene pan-cancer expression analysis survival analysis. peripheral blood individuals showed a positive correlation cfDNA. Neutrophil-derived reduced inhibitor exposure. These findings indicate actively involved CRC. thrombotic marker therapeutic prevent consequences cancer.

Language: Английский

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Neutrophil and Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 6 - 6

Published: Dec. 24, 2024

Colorectal cancer (CRC) is often associated with metastasis and recurrence the leading cause of cancer-related mortality. In progression CRC, recent studies have highlighted critical role neutrophils, particularly tumor-associated neutrophils (TANs). TANs both tumor-promoting tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, epithelial-to-mesenchymal transition. Tumor-promoting promote tumor growth by releasing proteases, reactive oxygen species, cytokines, whereas enhance immune responses activating T cells natural killer cells. Understanding mechanisms underlying TAN mobilization, plasticity, their in microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview biology CRC discusses functions neutrophils. Novel approaches targeting TANs, such as chemokine receptor antagonists, aim modulate neutrophil reprogramming offer promising avenues for improving treatment outcomes CRC.

Language: Английский

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Neutrophil extracellular traps modulate chemotherapy efficacy and its adverse side effects

Biology of the Cell, Journal Year: 2024, Volume and Issue: 116(7)

Published: May 9, 2024

Neutrophils, major regulator of innate immunity have recently emerged as key components the tumor microenvironment. The role neutrophils in cancer has been linked to their ability form neutrophil extracellular traps (NETs), structures composed decondensed DNA decorated with enzymes that are released into space. Here, we discuss pivotal roles NETs, influencing responses chemotherapy and its severe adverse effect. Highlighting recent insights, dual nature NETs context treatment, examining potential either counteract or enhance treatment outcomes. Strategic targeting emerges a promising avenue for determining combination therapies could help counteracting resistance enhancing efficacy well limiting complications due this type treatment.

Language: Английский

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Imaging and Therapy of Tumors Based on Neutrophil Extracellular Traps

Small Science, Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Neutrophil extracellular traps (NETs) formed by neutrophils are netlike scaffolds that mainly contain DNA and a variety of granule proteins. Many stimuli can lead to the NET formation through independent molecular pathways. Clinically, abundance NETs is correlated with poor tumor prognosis. The biological actions complex diverse, including promoting progression, awakening dormant cancer cells, resulting in immunosuppression support growth metastasis. Therefore, NET‐associated pathological processes provide an important clue for both diagnostic imaging alternative therapies many kinds cancers. In recent years, scientists’ efforts have focused on developing novel probes visualize therapeutic strategies degrading or inhibiting its block their pro‐tumoral functions. this review, development evaluation NETs‐targeted intervention progress therapy on.

Language: Английский

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