Assessing Functional Roles of the Senescence-Associated Secretory Phenotype (SASP)

Malaquin, Nicolas; Tu, Véronique

doi:10.1007/978-1-4939-8931-7_6

Cited by 23 publications

(17 citation statements)

References 34 publications

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“…However, based on their cytotoxic function they likely resemble myeloma-reactive T cells reported in the BM of MM patients (44) and may be pivotal to favorable clinical outcome in MM patients receiving MILs as adoptive T-cell therapy (45). These cells also adopt a secretory phenotype and produce large amounts of the inflammatory cytokines interferon-g (IFN-g) and tumor necrosis factor a (TNF-a) (Figure 1) (12) aligning with the previously described senescence-associate secretory phenotype (SASP) (46)(47)(48)(49).…”

Section: Significance Of Oligoclonal Expansion Of Cd8 + T Te Cells In Myelomasupporting

confidence: 58%

Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

et al. 2021

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The classical paradigm of host-tumor interaction, i.e. elimination, equilibrium, and escape (EEE), is reflected in the clinical behavior of myeloma which progresses from the premalignant condition, Monoclonal Gammopathy of Unknown Significance (MGUS). Despite the role of other immune cells, CD4+ regulatory T cells (Treg) and cytotoxic CD8+ T cells have emerged as the dominant effectors of host control of the myeloma clone. Progression from MGUS to myeloma is associated with alterations in Tregs and terminal effector CD8+ T cells (TTE). These changes involve CD39 and CD69 expression, affecting the adenosine pathway and residency in the bone marrow (BM) microenvironment, together with oligoclonal expansion within CD8+ TTE cells. In this mini-review article, in the context of earlier data, we summarize our recent understanding of Treg involvement in the adenosine pathway, the significance of oligoclonal expansion within CD8+ TTE cells and BM-residency of CD8+ TTE cells in MGUS and newly diagnosed multiple myeloma patients.

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Section: Significance Of Oligoclonal Expansion Of Cd8 + T Te Cells In Myelomasupporting

confidence: 58%

Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

et al. 2021

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“…In mice and humans, the senescence response prevents premalignant lesions from progressing to malignant cancers ( Krtolica et al., 2001 ). But senescent cells can also act as tumor-promoting agents ( Coppé et al., 2010 ; Lujambio, 2016 ; Sun et al., 2018 ), secreting factors that alter the tissue microenvironment; a feature called senescence-associated secretory phenotype (SASP) ( Malaquin et al., 2019 ). The long-term exposure to senescent cells is potentially detrimental, and their elimination may be fundamental for the treatment of cancer and other diseases ( Zhu et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

et al. 2021

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Summary Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.

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“…As mentioned earlier, these include chemokines, cytokines, metalloproteases, and growth factors which can act through both autocrine/paracrine pathways and can affect neighboring cells [115]. Although SASP is generally considered proinflammatory, the true microenvironmental impact and composition of SASP may vary according to cell types (i.e., fibroblasts/epithelial, normal/cancerous) and senescence-triggering stimuli (i.e., replicative senescence, DNA damage-induced senescence, oncogene-induced senescence) [14,116,117]. It is now evident that SASP functionally links senescence to various biological processes including tissue regeneration and remodeling, embryonic development, inflammation, and tumorigenesis.…”

Section: Cellular Senescence and The Role Of Saspsmentioning

confidence: 99%

The Emerging Role of Senescence in Ocular Disease

Sreekumar

Hinton

Kannan

2020

Oxidative Medicine and Cellular Longevity

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Cellular senescence is a state of irreversible cell cycle arrest in response to an array of cellular stresses. An important role for senescence has been shown for a number of pathophysiological conditions that include cardiovascular disease, pulmonary fibrosis, and diseases of the skin. However, whether senescence contributes to the progression of age-related macular degeneration (AMD) has not been studied in detail so far and the present review describes the recent research on this topic. We present an overview of the types of senescence, pathways of senescence, senescence-associated secretory phenotype (SASP), the role of mitochondria, and their functional implications along with antisenescent therapies. As a central mechanism, senescent cells can impact the surrounding tissue microenvironment via the secretion of a pool of bioactive molecules, termed the SASP. An updated summary of a number of new members of the ever-growing SASP family is presented. Further, we introduce the significance of mechanisms by which mitochondria may participate in the development of cellular senescence. Emerging evidence shows that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Based on recent studies, there is reasonable evidence that senescence could be a modifiable factor, and hence, it may be possible to delay age-related diseases by modulating basic aging mechanisms using SASP inhibitors/senolytic drugs. Thus, antisenescent therapies in aging and age-related diseases appear to have a promising potential.

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Assessing Functional Roles of the Senescence-Associated Secretory Phenotype (SASP)

Cited by 23 publications

References 34 publications

Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

The Emerging Role of Senescence in Ocular Disease

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