Phagocytosis,a vital defense mechanism,involves the recognition and elimination of foreign substances by cells.Phagocytes,such as neutrophils and macrophages,rapidly respond to invaders;macrophages are especially impo...Phagocytosis,a vital defense mechanism,involves the recognition and elimination of foreign substances by cells.Phagocytes,such as neutrophils and macrophages,rapidly respond to invaders;macrophages are especially important in later stages of the immune response.They detect“find me”signals to locate apoptotic cells and migrate toward them.Apoptotic cells then send“eat me”signals that are recognized by phagocytes via specific receptors.“Find me”and“eat me”signals can be strategically harnessed to modulate antitumor immunity in support of cancer therapy.These signals,such as calreticulin and phosphatidylserine,mediate potent pro-phagocytic effects,thereby promoting the engulfment of dying cells or their remnants by macrophages,neutrophils,and dendritic cells and inducing tumor cell death.This review summarizes the phagocytic“find me”and“eat me”signals,including their concepts,signaling mechanisms,involved ligands,and functions.Furthermore,we delineate the relationships between“find me”and“eat me”signaling molecules and tumors,especially the roles of these molecules in tumor initiation,progression,diagnosis,and patient prognosis.The interplay of these signals with tumor biology is elucidated,and specific approaches to modulate“find me”and“eat me”signals and enhance antitumor immunity are explored.Additionally,novel therapeutic strategies that combine“find me”and“eat me”signals to better bridge innate and adaptive immunity in the treatment of cancer patients are discussed.展开更多
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (...Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.展开更多
基金Shandong Provincial Laboratory Project,Grant/Award Number:SYS202202National Natural Science Foundation of China,Grant/Award Numbers:81972888,82272819+2 种基金Research Project of Jinan Microecological Biomedicine Shandong Laboratory,Grant/Award Numbers:JNL-202219B,JNL-202204A,JNL-2023017DJiangsu Provincial Key Research and Development Program,Grant/Award Number:BE2022840Nanjing University of Chinese Medicine,Grant/Award Number:2020YLXK007。
文摘Phagocytosis,a vital defense mechanism,involves the recognition and elimination of foreign substances by cells.Phagocytes,such as neutrophils and macrophages,rapidly respond to invaders;macrophages are especially important in later stages of the immune response.They detect“find me”signals to locate apoptotic cells and migrate toward them.Apoptotic cells then send“eat me”signals that are recognized by phagocytes via specific receptors.“Find me”and“eat me”signals can be strategically harnessed to modulate antitumor immunity in support of cancer therapy.These signals,such as calreticulin and phosphatidylserine,mediate potent pro-phagocytic effects,thereby promoting the engulfment of dying cells or their remnants by macrophages,neutrophils,and dendritic cells and inducing tumor cell death.This review summarizes the phagocytic“find me”and“eat me”signals,including their concepts,signaling mechanisms,involved ligands,and functions.Furthermore,we delineate the relationships between“find me”and“eat me”signaling molecules and tumors,especially the roles of these molecules in tumor initiation,progression,diagnosis,and patient prognosis.The interplay of these signals with tumor biology is elucidated,and specific approaches to modulate“find me”and“eat me”signals and enhance antitumor immunity are explored.Additionally,novel therapeutic strategies that combine“find me”and“eat me”signals to better bridge innate and adaptive immunity in the treatment of cancer patients are discussed.
文摘Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.
