Immunomodulation by ionizing radiation —impact for design of radio‐immunotherapies and for treatment of inflammatory diseases
Summary
Ionizing radiation is often regarded as an element of danger. But, danger responses on the cellular and molecular level are often beneficial with regard to the induction of anti‐tumor immunity and for amelioration of inflammation. We outline how in dependence of radiation dose and fraction, radiation itself—and especially in combination with immune modulators—impacts on the innate and adaptive immune system. Focus is set on radiation‐induced changes of the tumor cell phenotype and the cellular microenvironment including immunogenic cancer cell death. Mechanisms how anti‐tumor immune responses are triggere...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Benjamin Frey, Michael R ückert, Lisa Deloch, Paul F. Rühle, Anja Derer, Rainer Fietkau, Udo S. Gaipl Tags: INVITED REVIEW Source Type: research
Immune recognition of irradiated cancer cells
Summary
Ionizing irradiation has been extensively employed for the clinical management of solid tumors, with therapeutic or palliative intents, for decades. Until recently, radiation therapy (RT) was believed to mediate antineoplastic activity mostly (if not only) as a consequence of cancer cell‐intrinsic effects. Indeed, the macromolecular damage imposed to malignant cells by RT initiates one or multiple signal transduction cascades that drive a permanent proliferative arrest (cellular senescence) or regulated cell death. Both these phenomena show a rather linear dose‐response correlation. However, RT also mediates co...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Erik Wennerberg, Claire Vanpouille ‐Box, Sophia Bornstein, Takahiro Yamazaki, Sandra Demaria, Lorenzo Galluzzi Tags: INVITED REVIEW Source Type: research
Necroptotic cell death in anti ‐cancer therapy
Summary
Necroptosis is one the best‐characterized forms of regulated necrosis. Necroptosis is mediated by the kinase activities of receptor interacting protein kinase‐1 and receptor interacting protein kinase‐3, which eventually lead to the activation of mixed lineage kinase domain‐like. Necroptosis is characterized by rapid permeabilization of the plasma membrane, which is associated with the release of the cell content and subsequent exposure of damage‐associated molecular patterns (DAMPs) and cytokines/chemokines. This release underlies the immunogenic nature of necroptotic cancer cells and their ability to in...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Olga Krysko, Tania L øve Aaes, Valerian E. Kagan, Katharina D'Herde, Claus Bachert, Luc Leybaert, Peter Vandenabeele, Dmitri V. Krysko Tags: INVITED REVIEW Source Type: research
The renaissance of anti ‐neoplastic immunity from tumor cell demise
Summary
Cancer therapies can temporarily reduce tumor burdens by inducing malignant cell death. However, cancer cure is still far from realization because tumors often gain resistance to current treatment and eventually relapse. Accumulating evidence suggests that successful cancer interventions require anti‐tumor immunity. Therapy‐induced cell stress responses ultimately result in one or more cell death modalities, including apoptosis, autophagy, necroptosis, and pyroptosis. These irreversible dying processes are accompanied by active or passive release of cell death‐associated molecular patterns (CDAMPs), which can...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Yuting Ma, Jonathan M. Pitt, Qingqing Li, Heng Yang Tags: INVITED REVIEW Source Type: research
Danger signals: Chemotherapy enhancers?
Summary
Endogenous danger signals are molecules normally present in a given cell compartment that are rapidly released following cell stress and induce immune responses. We and others have shown that dying tumor cells treated with some chemotherapies are able to induce anticancer immune responses, which rely on their release of danger signals such as the nuclear protein HMGB1. DNA can also be released from chemotherapy‐treated tumor cells, act as a danger signal, and boost anticancer immunity. While the immunostimulatory properties of DNA have been identified for decades, the recent discovery of a novel family of recepto...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Thaiz Rivera Vargas, Lionel Apetoh Tags: INVITED REVIEW Source Type: research
Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance
Summary
Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the “eat‐me” signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells. Hence, both autophagy and poly...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Norma Bloy, Pauline Garcia, C éline M. Laumont, Jonathan M. Pitt, Antonella Sistigu, Gautier Stoll, Takahiro Yamazaki, Eric Bonneil, Aitziber Buqué, Juliette Humeau, Jan W. Drijfhout, Guillaume Meurice, Steffen Walter, Jens Fritsche, Toni Weinschenk, Ha Tags: INVITED REVIEW Source Type: research
Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment
Summary
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell‐derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis). To this end, apoptotic cells express specific eat‐me signals, such as externalized phosphatidyls...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Sushil Kumar, David Calianese, Raymond B. Birge Tags: INVITED REVIEW Source Type: research
Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses
Summary
The immunogenicity of cancer cells is an emerging determinant of anti‐cancer immunotherapy. Beyond developing immunostimulatory regimens like dendritic cell‐based vaccines, immune‐checkpoint blockers, and adoptive T‐cell transfer, investigators are beginning to focus on the immunobiology of dying cancer cells and its relevance for the success of anticancer immunotherapies. It is currently accepted that cancer cells may die in response to anti‐cancer therapies through regulated cell death programs, which may either repress or increase their immunogenic potential. In particular, the induction of immunogenic...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Abhishek D. Garg, Patrizia Agostinis Tags: INVITED REVIEW Source Type: research
The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis
Summary
Tissue damage frequently occurs. The immune system senses it and enforces homeostatic responses that lead to regeneration and repair. The synthesis of acute phase molecules is emerging as a crucial event in this program. The prototypic long pentraxin PTX3 orchestrates the recruitment of leukocytes, stabilizes the provisional matrix in order to facilitate leukocyte and stem progenitor cells trafficking, promotes swift and safe clearance of dying cells and of autoantigens, limiting autoimmunity and protecting the vasculature. These non‐redundant actions of PTX3 are necessary for the resolution of inflammation. Rece...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Marco Erreni, Angelo A. Manfredi, Cecilia Garlanda, Alberto Mantovani, Patrizia Rovere ‐Querini Tags: INVITED REVIEW Source Type: research
Metabolic regulation of macrophage phenotype and function
Summary
Studies in the last 20 years have given us a remarkable insight into the functional and phenotypic diversity of macrophages which reflects their integral role in host defence, homeostasis and pathogenesis. Mouse genetics, transcriptomic and epigenetic studies have provided an ontogenic and molecular perspective to the phenotypic diversity of these cells. Recently, metabolic studies have revealed the crucial role of metabolism and metabolites in shaping the phenotype and function of macrophages. Evidence pertaining to this aspect will be reviewed here. (Source: Immunological Reviews)
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Shilpi Saha, Irina N. Shalova, Subhra K. Biswas Tags: INVITED REVIEW Source Type: research
Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural killer cells to transformed and infected cells
Summary
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK‐activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by ...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: David H. Raulet, Assaf Marcus, Laurent Coscoy Tags: INVITED REVIEW Source Type: research
Extracellular nucleosides and nucleotides as immunomodulators
Summary
Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome‐mediated proinflammatory cascades. In contrast, the ectonucleotidase‐catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Oliver Kepp, Friedemann Loos, Peng Liu, Guido Kroemer Tags: INVITED REVIEW Source Type: research
High ‐mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair
Summary
A single protein, HMGB1, directs the triggering of inflammation, innate and adaptive immune responses, and tissue healing after damage. HMGB1 is the best characterized damage‐associated molecular pattern (DAMP), proteins that are normally inside the cell but are released after cell death, and allow the immune system to distinguish between antigens that are dangerous or not. Notably, cells undergoing severe stress actively secrete HMGB1 via a dedicated secretion pathway: HMGB1 is relocated from the nucleus to the cytoplasm and then to secretory lysosomes or directly to the extracellular space. Extracellular HMGB1 ...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Marco E. Bianchi, Massimo P. Crippa, Angelo A. Manfredi, Rosanna Mezzapelle, Patrizia Rovere Querini, Emilie Venereau Tags: INVITED REVIEW Source Type: research
Inflammatory cell death in intestinal pathologies
Summary
The intestinal tract is a site of intense immune cell activity that is poised to mount an effective response against a pathogen and yet maintain tolerance toward commensal bacteria and innocuous dietary antigens. The role of cell death in gut pathologies is particularly important as the intestinal epithelium undergoes self‐renewal every 4‐7 days through a continuous process of cell death and cell division. Cell death is also required for removal of infected, damaged, and cancerous cells. Certain forms of cell death trigger inflammation through release of damage‐associated molecular patterns. Further, molecul...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Deepika Sharma, Thirumala ‐Devi Kanneganti Tags: INVITED REVIEW Source Type: research
Alarmins and immunity
Summary
More than a decade has passed since the conceptualization of the “alarmin” hypothesis. The alarmin family has been expanding in terms of both number and the concept. It has recently become clear that alarmins play important roles as initiators and participants in a diverse range of physiological and pathophysiological processes such as host defense, regulation of gene expression, cellular homeostasis, wound healing, inflammation, allergy, autoimmunity, and oncogenesis. Here, we provide a general view on the participation of alarmins in the induction of innate and adaptive immune responses, as well as their cont...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: De Yang, Zhen Han, Joost J. Oppenheim Tags: INVITED REVIEW Source Type: research
