Secretome of senescent hepatoma cells modulate immune cell fate by macrophage polarization and neutrophil extracellular traps formation

Sen, Bijoya; Aggarwal, Savera; Nath, Rhisita; Sehgal, Rashi; Singh, Ravinder; Agrawal, Khushboo; Shashidhara, Ashwini Nagaraghatta; Rastogi, Archana; Bajpai, Meenu; Pamecha, Viniyendra; Trehanpati, Nirupma; Ramakrishna, Gayatri

doi:10.1007/s12032-022-01732-w

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…Their results are supported by an in vitro study showing polarization of macrophages by secretome from p53-positive hepatocytes. 31 Although M1 macrophages were not investigated in this study, this would be consistent with our previous work in which p53-positive tumors tended to be more common among CD163 high cases than in CD163 low cases (20% vs 8% p53-positive cases; P = .06 from Pearson χ 2 test), as well as our current results indicating that both CD163 and sCD163 are higher in patients with p53 aberrations.…”

Section: Discussionsupporting

confidence: 92%

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Nikkarinen¹,

Lokhande

Amini

et al. 2023

Blood Advances

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The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed towards the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). We aimed to investigate the prognostic value of sCD163 in 131 MCL patients. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) (p=0.002 and p<0.001) in 81 newly diagnosed chemoimmunotherapy-treated patients. The same was seen in a cohort of 50 relapsed MCL patients mainly treated within the phase II Philemon-trial with rituximab, ibrutinib and lenalidomide (PFS p=0.016 and OS p=0.035). In newly diagnosed patients with low levels of sCD163, five-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163 (r=0.64, p=0.014). The association with a poor prognosis was independent of MIPI, Ki67, p53 status and blastoid morphology, as assessed in a multivariable Cox proportional hazards model. Here, high sCD163 was associated with both shorter PFS (HR 3.48 95% CI: 1.42-8.54) and shorter OS (HR 4.33 95% CI: 1.32-14.2), showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify MCL patients with a very good prognosis.

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Section: Discussionsupporting

confidence: 92%

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Nikkarinen¹,

Lokhande

Amini

et al. 2023

Blood Advances

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“…Chemotherapy‐induced senescent cancer cells display phagocytic cell signature, engulf neighboring cells, and have a survival advantage 244 . Finally, senescent tumor cells educate immune cells in the microenvironment by polarizing macrophages and promoting the formation of neutrophil extracellular traps (NETs) 245 …”

Section: Neutrophils Bridge Aging and Cancermentioning

confidence: 99%

“…244 Finally, senescent tumor cells educate immune cells in the microenvironment by polarizing macrophages and promoting the formation of neutrophil extracellular traps (NETs). 245…”

Section: Parkinson's Diseasementioning

confidence: 99%

Neutrophils in aging and aging‐related pathologies

Avondt

Strecker

Tulotta

et al. 2022

Immunological Reviews

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Over the past millennia, life expectancy has drastically increased. While a mere 25 years during Bronze and Iron ages, life expectancy in many European countries and in Japan is currently above 80 years. Such an increase in life expectancy is a result of improved diet, life style, and medical care. Yet, increased life span and aging also represent the most important non-modifiable risk factors for several pathologies including cardiovascular disease, neurodegenerative diseases, and cancer. In recent years, neutrophils have been implicated in all of these pathologies. Hence, this review provides an overview of how aging impacts neutrophil production and function and conversely how neutrophils drive aging-associated pathologies. Finally, we provide a perspective on how processes of neutrophil-driven pathologies in the context of aging can be targeted therapeutically.

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“…Much less is known about the interaction between senescent cells and neutrophils, which are the first immune cells recruited to injured tissues. Neutrophils have been reported to target senescent cells during vascular remodeling in retinopathy [ 25 ] and to be influenced by the secretome of senescent hepatoma cells with contrasting results on neutrophil extracellular trap (NET) formation capacity [ 26 ]. Considering the increasing evidence of a prominent role of neutrophils in the tumor immune landscape, there is an urgent need to investigate the cross talk between senescent cells and neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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

Favaretto,

Rossi,

Cuollo

et al. 2024

Cancer Immunol Immunother

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

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Secretome of senescent hepatoma cells modulate immune cell fate by macrophage polarization and neutrophil extracellular traps formation

Cited by 7 publications

References 34 publications

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Neutrophils in aging and aging‐related pathologies

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

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