Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer

Bancaro, Nicoló; Calì, Bianca; Troiani, Martina; Elia, Angela Rita; Arzola, Rydell Alvarez; Attanasio, Giuseppe; Lai, Ping Shan; Gürel, Bora; Pereira, Rita; Guo, Christina; Mosole, Simone; Brina, Daniela; D’Ambrosio, Mariantonietta; Pasquini, Emiliano; Spataro, Clarissa; Zagato, Elena; Rinaldi, Andrea; Pedotti, Mattia; Lascio, Simona Di; Meani, Francesco; Montopoli, Monica; Ferrari, Matteo; Gallina, Andrea; Varani, L.; Mestre, Ricardo Pereira; Bolis, Marco; Sommer, S.; Bono, Johann de; Calcinotto, Arianna; Alimonti, Andrea

doi:10.1016/j.ccell.2023.02.004

Cited by 68 publications

(46 citation statements)

References 88 publications

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“…However, the appearance of a neutrophil sub-population expressing features of senescence (upregulation of p21, growth arrest, upregulation of BCL2 and/or BCL-XL) was unexpected, although perhaps not unprecedented, as a similar neutrophil population expressing features of senescence has recently been described in the setting of prostate cancer (38).…”

Section: Evidence For the Appearance Of Similar Injury-related Senesc...mentioning

confidence: 83%

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair

Saul,

Doolittle,

Rowsey

et al. 2024

Preprint

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Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells are key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings establish contextual roles of p21+ vs p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

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Section: Evidence For the Appearance Of Similar Injury-related Senesc...mentioning

confidence: 83%

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair

Saul,

Doolittle,

Rowsey

et al. 2024

Preprint

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“…22 They are vital in combating infectious diseases because they identify and engulf pathogens, release cytokines and free radicals, produce enzymes, and clear debris and necrotic tissue, thus boosting the immune response and guarding against infection. 23 Under normal circumstances, neutrophils in the circulation have a brief half-life (usually 7-12 hours) 24 ; however, their longevity is increased during the onset of sepsis. One key signaling pathway contributing to neutrophil resistance to apoptosis involves the activation of extracellular regulated protein kinases 1/2 and phosphoinositide-3 kinases in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammation response index as a prognostic factor for patients with sepsis-associated acute kidney injury: a retrospective observational study

Tang,

Zhong,

Nijiati

et al. 2024

J Int Med Res

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Objective To assess the association between the systemic inflammation response index (SIRI) and the prognosis in patients with sepsis-associated acute kidney injury (SA-AKI). Methods In this observational study, adult patients with SA-AKI were categorized into three groups based on SIRI tertiles. Survival outcomes were compared across the three groups using Kaplan–Meier survival curves. Various Cox proportional hazards regression models were developed to determine the association between the SIRI and mortality in patients with SA-AKI. Subgroup analyses were also performed to explore the association between different SIRI tertiles and all-cause mortality. Results After adjusting for several confounders, the second SIRI tertile (2.5 < SIRI < 7.6) was found to be an independent risk factor for 30-day mortality [hazard ratio (95% confidence interval): 1.19 (1.01–1.40)], 90-day mortality [1.22 (1.06–1.41)], and 365-day mortality [1.24 (1.09–1.40)]. Furthermore, high SIRI values were associated with increased risks of 30-day, 90-day, and 365-day mortality in patients with SA-AKI across all three models. The third tertile showed a significant association with adverse outcomes in most subgroups. Conclusions The SIRI serves as a comprehensive biomarker for predicting all-cause mortality of critically ill patients with SA-AKI.

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“…[154] Bancaro et al show that the HDAC inhibitor romidepsin kills senescent immunosuppressive neutrophils in a TREM2-dependent manner and, when administered in combination with a CXCR2 inhibitor, further inhibits prostate cancer progression by enhancing the efficacy of ENZA, a standard-ofcare for prostate cancer. [68] Neutrophils support lung colonization of metastasis-initiating breast cancer cells through leukotrienes. Inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) by zileuton abrogates the pro-metastatic activity of neutrophils and consequently reduces metastasis.…”

Section: Rvd1 Promoting Resolution Of Inflammationmentioning

confidence: 99%

“…Senescent‐like neutrophils are more immunosuppressive and tumor‐promoting than their canonical counterparts. [ 68 ] In summary, the important role of neutrophils in tumors suggests that targeting neutrophils may have potential therapeutic value.…”

Section: Neutrophils In Cancer: the Anti‐tumor And Pro‐tumor Paradigmmentioning

confidence: 99%

“…[ 154 ] Bancaro et al show that the HDAC inhibitor romidepsin kills senescent immunosuppressive neutrophils in a TREM2‐dependent manner and, when administered in combination with a CXCR2 inhibitor, further inhibits prostate cancer progression by enhancing the efficacy of ENZA, a standard‐of‐care for prostate cancer. [ 68 ]…”

Section: Targeting Neutrophils For Cancer Therapymentioning

confidence: 99%

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Engineering and Targeting Neutrophils for Cancer Therapy

Zhang,

Gu,

Wang

et al. 2024

Advanced Materials

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Neutrophils are the most abundant white blood cells in the circulation and act as the first line of defense against infections. Increasing evidence suggests that neutrophils possess heterogeneous phenotypes and functional plasticity in human health and diseases, including cancer. Neutrophils play multifaceted roles in cancer development and progression, and an N1/N2 paradigm of neutrophils in cancer has been proposed, where N1 neutrophils exert anti‐tumor properties while N2 neutrophils display tumor‐supportive and immune‐suppressive functions. Selective activation of beneficial neutrophil population and targeted inhibition or re‐polarization of tumor‐promoting neutrophils has shown an important potential in tumor therapy. In addition, due to the natural inflammation‐responsive and physical barrier‐crossing abilities, neutrophils and their derivatives (membranes and extracellular vesicles) are regarded as advanced drug delivery carriers for enhanced tumor targeting and improved therapeutic efficacy. In this review, we comprehensively presented the recent advances in engineering neutrophils for drug delivery and targeting neutrophils for remodeling tumor microenvironment. This review will provide a broad understanding of the potential of neutrophils in cancer therapy.This article is protected by copyright. All rights reserved

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Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer

Cited by 68 publications

References 88 publications

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair

Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair

Systemic inflammation response index as a prognostic factor for patients with sepsis-associated acute kidney injury: a retrospective observational study

Engineering and Targeting Neutrophils for Cancer Therapy

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