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Trends in Cancer Oct 2019Checkpoint blockade immunotherapy (CBT) has revolutionized cancer treatment; however, the cellular and molecular factors that govern responsiveness to immunotherapy... (Review)
Review
Checkpoint blockade immunotherapy (CBT) has revolutionized cancer treatment; however, the cellular and molecular factors that govern responsiveness to immunotherapy remain poorly understood. One emerging area of clinical importance is differential responsiveness to CBT across different tissue sites of tumor growth. Each tissue site in the body can contain unique tissue-resident immune cells from both the lymphoid and the myeloid compartment and differences in tissue-specific immune cell composition might predispose tumors in certain tissue sites to be more or less responsive to immunotherapy. Understanding the interplay between tissue-resident and systemic immune responses against tumors will help to determine how to better therapeutically target the immune system to fight cancer. This review summarizes clinical and preclinical investigations of tissue-specific antitumor immune responses and how they influence the tumor immune microenvironment and the efficacy of immunotherapy.
Topics: Animals; Biomarkers, Tumor; Dendritic Cells; Energy Metabolism; Humans; Immunity; Immunity, Innate; Immunotherapy; Molecular Targeted Therapy; Myeloid Cells; Neoplasm Staging; Neoplasms; Organ Specificity; T-Lymphocytes; Tumor Microenvironment
PubMed: 31706507
DOI: 10.1016/j.trecan.2019.07.006 -
Frontiers in Physiology 2022Honeybees () need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses....
Honeybees () need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously . We show that honeybees rely on two gustatory receptors to sense all relevant sugars.
PubMed: 36714315
DOI: 10.3389/fphys.2022.1089669 -
Exploration (Beijing, China) Dec 2022Nanomedicines are attractive paradigms to deliver drugs, contrast agents, immunomodulators, and gene editors for cancer therapy and diagnosis. However, the currently... (Review)
Review
Nanomedicines are attractive paradigms to deliver drugs, contrast agents, immunomodulators, and gene editors for cancer therapy and diagnosis. However, the currently developed nanomedicine suffers from poor serum stability, premature drug release, and lack of responsiveness. Crosslinking strategy can be utilized to overcome these shortcomings by employing stimuli-responsive chemical bonds to tightly hold the nanostructure and releasing the payloads spatiotemporally in a highly controlled manner. In this Review, we summarize the recently ingenious design of the stimuli-responsive crosslinked nanomedicines (SCN) in the field of cancer treatment and their advances in circumventing the drawbacks of the conventional drug delivery system. We classify the SCNs into three categories based on the crosslinking strategies, including built-in, on-surface, and inter-particle crosslinking nanomedicines. Thanks to the stimuli-responsive crosslinkages, SCNs are capable of keeping robust stability during systemic circulation. They also respond to the particular tumoral conditions to experience a series of dynamic changes, such as the changes in size, surface charge, targeting moieties, integrity, and imaging signals. These characteristics allow them to efficiently overcome different biological barriers and substantially improve the drug delivery efficiency, tumor-targeting ability, and imaging sensitivities. With the examples discussed, we envision that our perspectives can inspire more attempts to engineer intelligent nanomedicine to achieve effective cancer therapy and diagnosis.
PubMed: 37324805
DOI: 10.1002/EXP.20210134 -
Chemical Science Nov 2023Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the... (Review)
Review
Ultrasound (US) is routinely used for diagnostic imaging and increasingly employed for therapeutic applications. Materials that act as cavitation nuclei can improve the resolution of US imaging, and facilitate therapeutic US procedures by promoting local drug delivery or allowing temporary biological barrier opening at moderate acoustic powers. Polymeric materials offer a high degree of control over physicochemical features concerning responsiveness to US, tuning chain composition, length and rigidity. This level of control cannot be achieved by materials made of lipids or proteins. In this perspective, we present key engineered polymeric materials that respond to US, including microbubbles, gas-stabilizing nanocups, microcapsules and gas-releasing nanoparticles, and discuss their formulation aspects as well as their principles of US responsiveness. Focusing on microbubbles as the most common US-responsive polymeric materials, we further evaluate the available chemical toolbox to engineer polymer shell properties and enhance their performance in US imaging and US-mediated drug delivery. Additionally, we summarize emerging applications of polymeric microbubbles in molecular imaging, sonopermeation, and gas and drug delivery, based on refinement of MB shell properties. Altogether, this manuscript provides new perspectives on US-responsive polymeric designs, envisaging their current and future applications in US imaging and therapy.
PubMed: 37969594
DOI: 10.1039/d3sc04339h -
Interdisciplinary Topics in Gerontology... 2020The collective loss of immune protection during aging leads to poor vaccine responses and an increased severity of infection for the elderly. Here, we review our current... (Review)
Review
The collective loss of immune protection during aging leads to poor vaccine responses and an increased severity of infection for the elderly. Here, we review our current understanding of effects of aging on the cellular and molecular dysregulation of innate immune cells as well as the relevant tissue milieu which influences their functions. The innate immune system is composed of multiple cell types which provide distinct and essential roles in tissue surveillance and antigen presentation as well as early responses to infection or injury. Functional defects that arise during aging lead to a reduced dynamic range of responsiveness, altered cytokine dynamics, and impaired tissue repair. Heightened inflammation influences both the dysregulation of innate immune responses as well as surrounding tissue microenvironments which have a critical role in development of a functional immune response. In particular, age-related physical and inflammatory changes in the skin, lung, lymph nodes, and adipose tissue reflect disrupted architecture and spatial organization contributing to diminished immune responsiveness. Underlying mechanisms include altered transcriptional programming and dysregulation of critical innate immune signaling cascades. Further, we identify signaling functions of bioactive lipid mediators which address chronic inflammation and may contribute to the resolution of inflammation to improve innate immunity during aging.
Topics: Aged; Aging; Humans; Immunity, Innate; Inflammation; Lung; Lymph Nodes; Skin; Vaccination
PubMed: 32294641
DOI: 10.1159/000504480 -
Frontiers in Cellular and Infection... 2017Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a... (Review)
Review
Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.
Topics: Apoptosis; Cell Adhesion; Chemokines; Chemotaxis; Cytokines; Exocytosis; Extracellular Traps; Extracellular Vesicles; Humans; Immunity, Innate; Lipid Metabolism; NADPH Oxidases; Neutrophils; Phagocytosis; Phenotype; Reactive Oxygen Species; Respiratory Burst
PubMed: 28611952
DOI: 10.3389/fcimb.2017.00217 -
Trends in Biochemical Sciences Nov 2023Biomembranes are complex materials composed of lipids and proteins that compartmentalize biochemistry. They are actively remodeled in response to physical and metabolic... (Review)
Review
Biomembranes are complex materials composed of lipids and proteins that compartmentalize biochemistry. They are actively remodeled in response to physical and metabolic cues, as well as during cell differentiation and stress. The concept of homeoviscous adaptation has become a textbook example of membrane responsiveness. Here, we discuss limitations and common misconceptions revolving around it. By highlighting key moments in the life cycle of a transmembrane protein, we illustrate that membrane thickness and a finely regulated membrane compressibility are crucial to facilitate proper membrane protein insertion, function, sorting, and inheritance. We propose that the unfolded protein response (UPR) provides a mechanism for endoplasmic reticulum (ER) membrane homeostasis by sensing aberrant transverse membrane stiffening and triggering adaptive responses that re-establish membrane compressibility.
Topics: Endoplasmic Reticulum Stress; Unfolded Protein Response; Homeostasis; Endoplasmic Reticulum; Membrane Proteins
PubMed: 37652754
DOI: 10.1016/j.tibs.2023.08.004 -
Chemical Science Feb 2021Cancer immunotherapy is a revolutionary treatment method in oncology, which uses a human's own immune system against cancer. Many immunomodulators that trigger an immune... (Review)
Review
Cancer immunotherapy is a revolutionary treatment method in oncology, which uses a human's own immune system against cancer. Many immunomodulators that trigger an immune response have been developed and applied in cancer immunotherapy. However, there is the risk of causing an excessive immune response upon directly injecting common immunomodulators into the human body to trigger an immune response. Therefore, the development of intelligent stimuli-responsive immunomodulators to elicit controlled immune responses in cancer immunotherapy is of great significance. Nanotechnology offers the possibility of designing smart nanomedicine to amplify the antitumor response in a safe and effective manner. Progress relating to intelligent stimuli-responsive nano immunomodulators for cancer immunotherapy is highlighted as a new creative direction in the field. Considering the clinical demand for cancer immunotherapy, we put forward some suggestions for constructing new intelligent stimuli-responsive nano immunomodulators, which will advance the development of cancer immunotherapy.
PubMed: 34164080
DOI: 10.1039/d0sc06557a