Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages

Petrovski, Goran; Ayna, Gizem; Májai, Gyöngyike; Hodrea, Judit; Benkő, Szilvia; Mádi, András; Fésüs, László

doi:10.4161/auto.7.3.14583

Cited by 59 publications

(48 citation statements)

References 32 publications

(48 reference statements)

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“…68 Radiotherapy triggers ATP release from dying tumor cells through its interaction with the P2 Â 7 purinergic receptor, 69 possibly resulting in the activation of the NLRP3-ASC-inflammasome axis and subsequent secretion of IL-1b. 70 We and others recently showed that oncolytic viruses induce secretion of extracellular ATP from human cancer cells (Figure 1). 9,65 Unlike ecto-CRT induction, the release of ATP and HMGB1 is triggered by a range of death-inducing stimuli, and is not restricted to induction in apoptotic cell death.…”

Section: Adenosine Triphosphatementioning

confidence: 95%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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Section: Adenosine Triphosphatementioning

confidence: 95%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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“…12,23 DC inflammasome activation results in the synthesis and secretion of IL-1β, where secreted IL-1β initiates further proinflammatory events. 12,23,26 In addition to the classic components of ICD, other molecules upregulated in response to radiotherapy have been shown to be involved in antitumor immunity. For example, major histocompatibility complex Class I molecules present endogenous peptides to cytotoxic T lymphocytes and allows for the recognition of tumor cells by cytotoxic T lymphocytes, resulting in efficient tumor cell kill.…”

Section: Immunogenic Cell Deathmentioning

confidence: 99%

Radiotherapy and Immunogenic Cell Death

Golden

Apétoh

2015

Seminars in Radiation Oncology

373

251

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Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. 1), is one such exploitable process that contributes to the propagation of antitumor immunity. Downstream components of the immune system may suppress, promote, or ambiguously affect antitumoral responses. Additionally, host, tumor, and treatment-related characteristics govern the significance of these signals, thereby dictating therapeutic outcomes. Herein, we review the process of radiotherapy-induced immunogenic cell death and its role in generating an in situ vaccine to help refine radioimmunotherapy-based protocols.

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“…[36][37][38] In another context, autophagic dying cells have been found to undergo (phosphatidylserine (PtdSer)-based) 8 phagocytosis associated with inflammatory response. 39 Thus in the future it would be crucial to identify the molecular determinants driving the recognition and phagocytic removal of cancer cells dying through these non-apoptotic pathways.…”

Section: Regulated Necrosismentioning

confidence: 99%

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

et al. 2016

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Phagocytosis of dying cells is a major homeostatic process that represents the final stage of cell death in a tissue context. Under basal conditions, in a diseased tissue (such as cancer) or after treatment with cytotoxic therapies (such as anticancer therapies), phagocytosis has a major role in avoiding toxic accumulation of cellular corpses. Recognition and phagocytosis of dying cancer cells dictate the eventual immunological consequences (i.e., tolerogenic, inflammatory or immunogenic) depending on a series of factors, including the type of 'eat me' signals. Homeostatic clearance of dying cancer cells (i.e., tolerogenic phagocytosis) tends to facilitate pro-tumorigenic processes and actively suppress antitumour immunity. Conversely, cancer cells killed by immunogenic anticancer therapies may stimulate non-homeostatic clearance by antigen-presenting cells and drive cancer antigen-directed immunity. On the other hand, (a general) inflammatory clearance of dying cancer cells could have pro-tumorigenic or antitumorigenic consequences depending on the context. Interestingly, the immunosuppressive consequences that accompany tolerogenic phagocytosis can be reversed through immune-checkpoint therapies. In the present review, we discuss the pivotal role of phagocytosis in regulating responses to anticancer therapy. We give particular attention to the role of phagocytosis following treatment with immunogenic or immune-checkpoint therapies, the clinical prognostic and predictive significance of phagocytic signals for cancer patients and the therapeutic strategies that can be employed for direct targeting of phagocytic determinants.

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Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages

Cited by 59 publications

References 32 publications

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Radiotherapy and Immunogenic Cell Death

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

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