Volume 5 (2021)
Innate RIG-I signaling restores antigen presentation in tumors and overcomes T cell resistance
Beatrice Thier1,2 and Annette Paschen1,2
In recent years, therapy with immune modulating antibodies, termed immune checkpoint blockade (ICB), has revolutionized the treatment of advanced metastatic melanoma, yielding long-lasting clinical responses in a subgroup of patients. But despite this remarkable progress, resistance to therapy represents a major clinical challenge. ICB efficacy is critically dependent on cytotoxic CD8+ T cells targeting tumor cells in an HLA class I (HLA-I) antigen-dependent manner. Transcriptional suppression of the HLA-I antigen processing and presentation machinery (HLA-I APM) in melanoma cells leads to HLA-I-low/-negative tumor cell phenotypes escaping CD8+ T cell recognition and contributing to ICB resistance. In general, HLA-I-low/-negative tumor cells can be re-sensitized to T cells by interferons (IFN), augmenting HLA-I APM expression. However, this mechanism fails when melanoma cells acquire resistance to IFN, which recently turned out as a key resistance mechanism in (...)
To promote or inhibit glioma progression, that is the question for IL-33
Stephen M. Robbins1 and Donna L. Senger1
Glioblastoma represents one of the most fatal of human cancers. Although there has been progress in the treatment of glioblastoma as a result of a treatment regimen that combines maximal
PDLIM1: Structure, function and implication in cancer
Jian-Kang Zhou1, Xin Fan1, Jian Cheng1,2, Wenrong Liu1 and Yong Peng1
PDLIM1, a member of the PDZ-LIM family, is a cytoskeletal protein and functions as a platform to form distinct protein complexes, thus participating in multiple physiological processes such as cytoskeleton regulation and synapse formation. Emerging evidence demonstrates that PDLIM1 is dysregualted in a variety of tumors and plays essential roles in tumor initiation and progression. In this review, we summarize the structure and function of PDLIM1, as well as its important roles in human cancers.
Towards a better understanding of the neuro-developmental role of autophagy in sickness and in health
Juan Zapata-Muñoz1, Beatriz Villarejo-Zori1, Pablo Largo-Barrientos2 and Patricia Boya1
Autophagy is a critical cellular process by which biomolecules and cellular organelles are degraded in an orderly manner inside lysosomes. This process is particularly important in neurons: these post-mitotic cells cannot divide or be easily replaced and are therefore especially sensitive to the accumulation of toxic proteins and damaged organelles. Dysregulation of neuronal autophagy is well documented in a range of neurodegenerative diseases. However, growing evidence indicates that autophagy also critically contributes to neurodevelopmental cellular processes, including neurogenesis, maintenance of neural stem cell homeostasis, differentiation, metabolic reprogramming, and synaptic remodelling. These findings implicate autophagy in neurodevelopmental disorders. In this review we discuss the current understanding of the role of autophagy in neurodevelopment and neurodevelopmental disorders, as well as currently available tools and techniques that (...)
Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease
Srinivasa Subramaniam1
The symptoms of HD, a neurodegenerative disorder, are severe disruption of cognitive and motor functions, including changes in posture and gait. HTT, the gene responsible for HD, is CAG (codes
The evolution of the concept of stress and the framework of the stress system
Siyu Lu1, Fang Wei1,2 and Guolin Li1,2,3
Stress is a central concept in biology and has now been widely used in psychological, physiological, social, and even environmental fields. However, the concept of stress was cross-utilized to refer to different elements of the stress system including stressful stimulus, stressor, stress response, and stress effect. Here, we summarized the evolution of the concept of stress and the framework of the stress system. We find although the concept of stress is developed from Selye’s “general adaptation syndrome”, it has now expanded and evolved significantly. Stress is now defined as a state of homeostasis being challenged, including both system stress and local stress. A specific stressor may potentially bring about specific local stress, while the intensity of stress beyond a threshold may commonly activate the hypothalamic-pituitary-adrenal axis and result in a systematic stress response. The framework of the stress system indicates that stress includes three types: (...)
Coping with the calcium overload caused by cell injury: ER to the rescue
Goutam Chandra1,2, Davi A. G. Mázala1,3 and Jyoti K. Jaiswal1,4
It was nearly a century ago that Lewis Victor Heilbrunn identified the requirement of extracellular Ca2+ for what he termed as ‘surface precipitation reaction‘, a process that allows the cytoplasm
Coping with the calcium overload caused by cell injury: ER to the rescue
Goutam Chandra1,2, Davi A. G. Mázala1,3 and Jyoti K. Jaiswal1,4
It was nearly a century ago that Lewis Victor Heilbrunn identified the requirement of extracellular Ca2+ for what he termed as ‘surface precipitation reaction‘, a process that allows the cytoplasm
Inhibitory DAMPs in immunogenic cell death and its clinical implications
Kazukuni Hayashi1,2, Fotis Nikolos3 and Keith S. Chan1,3
– [table id=388/] INHIBITORY DAMP OR INHIBITORY DAMPS? How are immunostimulatory DAMPs shut off? Under normal physiological conditions, the co-stimulatory molecules, CD80/86, on antigen presenting cells bind to the co-activating
Roles of phosphatidyl inositol 3 kinase gamma (PI3Kγ) in respiratory diseases
Valentina Sala1, Angela Della Sala1, Alessandra Ghigo1,2,# and Emilio Hirsch1,2,#
Phosphatidyl inositol 3 kinase gamma (PI3Kγ) is expressed in all the cell types that are involved in airway inflammation and disease, including not only leukocytes, but also structural cells, where it is expressed at very low levels under physiological conditions, while is significantly upregulated after stress. In the airways, PI3Kγ behaves as a trigger or a controller, depending on the pathological context. In this review, the contribution of PI3Kγ in a plethora of respiratory diseases, spanning from acute lung injury, pulmonary fibrosis, asthma, cystic fibrosis and response to both bacterial and viral pathogens, will be commented.
The OFD1 protein is a novel player in selective autophagy: another tile to the cilia/autophagy puzzle
Manuela Morleo1 and Brunella Franco1,2
Autophagy is an evolutionary conserved and highly regulated cellular degradation pathway which entails the engulfment of cellular components into double-membrane vesicles, called autophagosomes, which then fuse with lysosomes to degrade
Innate RIG-I signaling restores antigen presentation in tumors and overcomes T cell resistance
Beatrice Thier1,2 and Annette Paschen1,2
In recent years, therapy with immune modulating antibodies, termed immune checkpoint blockade (ICB), has revolutionized the treatment of advanced metastatic melanoma, yielding long-lasting clinical responses in a subgroup of patients. But despite this remarkable progress, resistance to therapy represents a major clinical challenge. ICB efficacy is critically dependent on cytotoxic CD8+ T cells targeting tumor cells in an HLA class I (HLA-I) antigen-dependent manner. Transcriptional suppression of the HLA-I antigen processing and presentation machinery (HLA-I APM) in melanoma cells leads to HLA-I-low/-negative tumor cell phenotypes escaping CD8+ T cell recognition and contributing to ICB resistance. In general, HLA-I-low/-negative tumor cells can be re-sensitized to T cells by interferons (IFN), augmenting HLA-I APM expression. However, this mechanism fails when melanoma cells acquire resistance to IFN, which recently turned out as a key resistance mechanism in (...)
Spermidine supplementation in rare translation-associated disorders
Andreas Zimmermann1,2, Didac Carmona-Gutierrez1, and Frank Madeo1,2,3
Spermidine is a naturally occurring polyamine that is strongly involved in manifold cellular processes, for example, DNA, RNA and protein stabilization, cell growth, proliferation, autophagy, and aging. Importantly, spermidine has