AIM: To examine the genetic profile of primary uveal melanoma (UM) as compared to UM in immune escape.METHODS: Dendritic cells (DC) loaded with lysates of UM cells of high metastatic potential were used to stimulate C...AIM: To examine the genetic profile of primary uveal melanoma (UM) as compared to UM in immune escape.METHODS: Dendritic cells (DC) loaded with lysates of UM cells of high metastatic potential were used to stimulate CTLs(CTLs). When CTLs co-cultured with the UM cells, most UM cells could be eliminated. Survival UM cells grew slowly and were considered to be survival variants and examined by a microarray analysis. These differential genes were analyzed further with Venn Diagrams and functions related to immune escape. We additionally examined transcriptional changes of manually selected survival variants of UM cells and of clinical UM samples by quantitative real-time polymerase chain reaction (qRT-PCR), and analyzed the correlation of these expressions and patients’ survival.RESULTS: Gene expression analyses revealed a marked up-regulation of SLAMF7 and CCL22 and a significant down-regulation of KRT10, FXYD3 and ABCC2. The expression of these genes in the relapsed UM was significantly greater than those in primary UM. UM patients with overexpression of these genes had a shorter survival period as compared with those of their underexpression.CONCLUSION: Gene expression, in particular of SLAMF7, CCL22, KRT10, FXYD3 and ABCC2, differed between primary UM cells and survival variants of UM cells.展开更多
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
基金Supported by National Natural Science Foundation of China(No.81570891No.81272981)+4 种基金the Beijing Municipal Administration of Hospitals'Ascent Plan(No.DFL20150201)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z151100001615052)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.ZYLX201307)Beijing Natural Science Foundation(No.7151003)Advanced Health Care Professionals Development Project of Beijing Municipal Health Bureau(No.2014-2-003)
文摘AIM: To examine the genetic profile of primary uveal melanoma (UM) as compared to UM in immune escape.METHODS: Dendritic cells (DC) loaded with lysates of UM cells of high metastatic potential were used to stimulate CTLs(CTLs). When CTLs co-cultured with the UM cells, most UM cells could be eliminated. Survival UM cells grew slowly and were considered to be survival variants and examined by a microarray analysis. These differential genes were analyzed further with Venn Diagrams and functions related to immune escape. We additionally examined transcriptional changes of manually selected survival variants of UM cells and of clinical UM samples by quantitative real-time polymerase chain reaction (qRT-PCR), and analyzed the correlation of these expressions and patients’ survival.RESULTS: Gene expression analyses revealed a marked up-regulation of SLAMF7 and CCL22 and a significant down-regulation of KRT10, FXYD3 and ABCC2. The expression of these genes in the relapsed UM was significantly greater than those in primary UM. UM patients with overexpression of these genes had a shorter survival period as compared with those of their underexpression.CONCLUSION: Gene expression, in particular of SLAMF7, CCL22, KRT10, FXYD3 and ABCC2, differed between primary UM cells and survival variants of UM cells.
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.
