An Immunogenic Cell Death-Related Classification Predicts Prognosis and Response to Immunotherapy in Head and Neck Squamous Cell Carcinoma

Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients

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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000337 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000337 ◽

Cited By ~ 56

Author(s):

Lorenzo Galluzzi ◽

Ilio Vitale ◽

Sarah Warren ◽

Sandy Adjemian ◽

Patrizia Agostinis ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Adaptive Immune Response ◽

Operational Definition ◽

Immunogenic Cell Death ◽

Adaptive Immune ◽

Regulated Cell Death ◽

Definition Of

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

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Immunogenic Cell Death and Elimination of Immunosuppressive Cells: A Double-Edged Sword of Chemotherapy

Cancers ◽

10.3390/cancers12092637 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2637 ◽

Cited By ~ 1

Author(s):

Jean-David Fumet ◽

Emeric Limagne ◽

Marion Thibaudin ◽

Francois Ghiringhelli

Keyword(s):

Immune Response ◽

Cell Death ◽

Immune Escape ◽

Adaptive Immune Response ◽

Immunogenic Cell Death ◽

Regulated Cell Death ◽

Immunological Effects ◽

Current Area ◽

Immunosuppressive Cells ◽

Main Effects

Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials.

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Abstract 3734: Cancer cell-targeted photoimmunotherapy elicits immunogenic cell death and activates the innate and adaptive immune response in the tumor microenvironment

10.1158/1538-7445.am2019-3734 ◽

2019 ◽

Author(s):

Michelle A. Hsu ◽

Stephanie M. Okamura ◽

Daniele M. Bergeron ◽

Deepak Yadav ◽

Jerry J. Fong ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Tumor Microenvironment ◽

Cancer Cell ◽

Adaptive Immune Response ◽

Immunogenic Cell Death ◽

Adaptive Immune

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Radiotherapy as a Backbone for Novel Concepts in Cancer Immunotherapy

Cancers ◽

10.3390/cancers12010079 ◽

2019 ◽

Vol 12 (1) ◽

pp. 79 ◽

Cited By ~ 5

Author(s):

Julijan Kabiljo ◽

Felix Harpain ◽

Sebastian Carotta ◽

Michael Bergmann

Keyword(s):

Cell Death ◽

Clinical Studies ◽

Checkpoint Inhibitors ◽

External Beam Radiotherapy ◽

Local Treatment ◽

Immunogenic Cell Death ◽

Immune Microenvironment ◽

Anti Cancer ◽

Tumor Immune Microenvironment ◽

Radiation Induced

Radiation-induced immunogenic cell death has been described to contribute to the efficacy of external beam radiotherapy in local treatment of solid tumors. It is well established that radiation therapy can induce immunogenic cell death in cancer cells under certain conditions. Initial clinical studies combining radiotherapy with immunotherapies suggest a synergistic potential of this approach. Improving our understanding of how radiation reconditions the tumor immune microenvironment should pave the way for designing rational and robust combinations with immunotherapeutic drugs that enhance both local and systemic anti-cancer immune effects. In this review, we summarize irradiation-induced types of immunogenic cell death and their effects on the tumor microenvironment. We discuss preclinical insights on mechanisms and benefits of combining radiotherapy with immunotherapy, focusing on immune checkpoint inhibitors. In addition, we elaborate how these observations were translated into clinical studies and which parameters may be optimized to achieve best results in future clinical trials.

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Natural Compounds of Marine Origin as Inducers of Immunogenic Cell Death (ICD): Potential Role for Cancer Interception and Therapy

Cells ◽

10.3390/cells10020231 ◽

2021 ◽

Vol 10 (2) ◽

pp. 231

Author(s):

Clementina Sansone ◽

Antonino Bruno ◽

Concetta Piscitelli ◽

Denisa Baci ◽

Angelo Fontana ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Immune System ◽

Immune Cell ◽

Cytotoxic T Cells ◽

Immunogenic Cell Death ◽

Type I ◽

Bioactive Natural Products ◽

Signalling Molecules ◽

Major Factors

Regulated cell death (RCD) has always been considered a tolerogenic event. Immunogenic cell death (ICD) occurs as a consequence of tumour cell death accompanied by the release of damage-associated molecular patterns (DAMPs), triggering an immune response. ICD plays a major role in stimulating the function of the immune system in cancer during chemotherapy and radiotherapy. ICD can therefore represent one of the routes to boost anticancer immune responses. According to the recommendations of the Nomenclature Committee on Cell Death (2018), apoptosis (type I cell death) and necrosis (type II cell death) represent are not the only types of RCD, which also includes necroptosis, pyroptosis, ferroptosis and others. Specific downstream signalling molecules and death-inducing stimuli can regulate distinct forms of ICD, which develop and promote the immune cell response. Dying cells deliver different potential immunogenic signals, such as DAMPs, which are able to stimulate the immune system. The acute exposure of DAMPs can prime antitumour immunity by inducing activation of antigen-presenting cells (APC), such as dendritic cells (DC), leading to the downstream response by cytotoxic T cells and natural killer cells (NK). As ICD represents an important target to direct and develop new pharmacological interventions, the identification of bioactive natural products, which are endowed with low side effects, higher tolerability and preferentially inducing immunogenic programmed cell death, represents a priority in biomedical research. The ability of ICD to drive the immune response depends on two major factors, neither of which is intrinsic to cell death: ‘Antigenicity and adjuvanticity’. Indeed, the use of natural ICD-triggering molecules, alone or in combination with different (immuno)therapies, can result in higher efficacy and tolerability. Here, we focused on natural (marine) compounds, particularly on marine microalgae derived molecules such as exopolysaccharides, sulphated polysaccharides, glycopeptides, glycolipids, phospholipids, that are endowed with ICD-inducing properties and sulfavants. Here, we discuss novel and repurposed small-molecule ICD triggers, as well as their ability to target important molecular pathways including the IL-6, TNF-α and interferons (IFNs), leading to immune stimulation, which could be used alone or in combinatorial immunotherapeutic strategies in cancer prevention and therapies.

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Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

Journal of Materials Chemistry B ◽

10.1039/d1tb00397f ◽

2021 ◽

Author(s):

Suah Yang ◽

In-Cheol Sun ◽

Hee Sook Hwang ◽

Man Kyu Shim ◽

Hong Yeol Yoon ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Cancer Immunotherapy ◽

Potential Application ◽

Adaptive Immune Response ◽

Immunogenic Cell Death ◽

Living Body ◽

Adaptive Immune ◽

Physical Stimuli ◽

Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

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618 Vedotin ADCs induce ER stress and elicit hallmarks of ICD across multiple cancer indications

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0618 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A654-A654

Author(s):

Kerry Klussman ◽

Elena-Marie Tenn ◽

Shaylin Higgins ◽

Rebecca Mazahreh ◽

Katie Snead ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Stress Response ◽

Cell Surface ◽

Er Stress ◽

Immune Cell ◽

Adaptive Immune Response ◽

Cytotoxic Agents ◽

Er Stress Response ◽

Adaptive Immune

BackgroundEffective cancer treatment requires durable elimination of malignant cells. Cytotoxic chemotherapeutic agents used to treat cancer often show initial anti-tumor efficacy, but fail to produce long-term durable responses in patients. The elicitation of durable responses and improved survival in response to cytotoxic agents may be associated with the induction of innate and adaptive immune response to the cancer. For example, tumor cells undergoing apoptosis following exposure to some cytotoxic agents emit immunostimulatory damage-associated molecular patterns (DAMPs), this form of cell death is termed immunogenic cell death (ICD). ICD can promote the recruitment and activation of both the innate and adaptive immune system, providing an additional mechanism to drive an anti-tumor response.MethodsVedotin-based antibody drug conjugates (ADCs) drive cytotoxicity in tumor cells by engaging tumor antigens on the cell surface, internalizing with the cell surface antigen, and delivering monomethyl auristatin E (MMAE) payload. Following intracellular delivery, MMAE induces mitotic arrest, as well as an endoplasmic reticulum (ER) stress response resulting from microtubule disruption. Following tumor cell treatment, indicators of the ER stress response are observed with vedotin-based ADCs including induction of phospho-JNK and CHOP, This mechanism of MMAE induced ER stress results in emission of hallmark ICD DAMPs including cell-surface calreticulin, extracellular release of HMGB1 and ATP. In this presentation we highlight the ability of MMAE to induce the hallmarks of ICD in multiple cancers across different tissue origins using distinct valine-citrulline-MMAE (vedotin)-based ADCs.ResultsThe culmination of these ICD hallmarks resulted in innate immune cell activation in vitro and in vivo in mouse xenograft models. Tumor bearing mice treated with vedotin-based ADCs resulted in the promotion of immune cell recruitment and activation in tumors. Analysis of immune activation by vedotin-based ADCs included production of innate cytokines and upregulation of HLA/MHC-Class I/II expression, which supports a role in activating both the innate and adaptive immune response. To further our understanding of the potent and broad ability of vedotin ADCs to induce ICD, we have also begun to examine the ICD potential of different classes of ADC payloads including other microtubule inhibitors (auristatins and maytansines), and DNA damaging agents (DNA alkylators or topoisomerase inhibitors). Initial data indicate differences in ICD induction by these agents.ConclusionsThese results help build the rationale for vedotin-based ADCs as preferred partners for immune checkpoint blockade agents.Ethics ApprovalStudies with human samples were performed according to institutional ethics standards. Animal studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029.

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