查看更多>>摘要：Macrophages are critical regulators of tissue homeostasis but are also abundant in the tumor microenvironment(TME).In both primary tumors and metastases,such tumor-associated macrophages(TAMs)seem to support tumor development.While we know that TAMs are the dominant immune cells in the TME,their vast heterogeneity and associated functions are only just being unraveled.In this review,we outline the various known TAM populations found thus far and delineate their specialized roles associated with the main stages of cancer progression.We discuss how macrophages may prime the premetastatic niche to enable the growth of a metastasis and then how subsequent metastasis-associated macrophages can support secondary tumor growth.Finally,we speculate on the challenges that remain to be overcome in TAM research.
查看更多>>摘要：Neutrophils,as the first defenders against external microbes and stimuli,are highly active and finely regulated innate immune cells.Emerging evidence has challenged the conventional dogma that neutrophils are a homogeneous population with a short lifespan that promotes tissue damage.Recent findings on neutrophil diversity and plasticity in homeostatic and disease states have centered on neutrophils in the circulation.In contrast,a comprehensive understanding of tissue-specialized neutrophils in health and disease is still lacking.This article will first discuss how multiomics advances have contributed to our understanding of neutrophil heterogeneity and diversification in resting and pathological settings.This discussion will be followed by a focus on the heterogeneity and role of neutrophils in solid organ transplantation and how neutrophils may contribute to transplant-related complications.The goal of this article is to provide an overview of the research on the involvement of neutrophils in transplantation,with the aim that this may draw attention to an underappreciated area of neutrophil research.
查看更多>>摘要：Balanced immunity is pivotal for health and homeostasis.CD4+ helper T(Th)cells are central to the balance between immune tolerance and immune rejection.Th cells adopt distinct functions to maintain tolerance and clear pathogens.Dysregulation of Th cell function often leads to maladies,including autoimmunity,inflammatory disease,cancer,and infection.Regulatory T(Treg)and Th17 cells are critical Th cell types involved in immune tolerance,homeostasis,pathogenicity,and pathogen clearance.It is therefore critical to understand how Treg and Th17 cells are regulated in health and disease.Cytokines are instrumental in directing Treg and Th17 cell function.The evolutionarily conserved TGF-β(transforming growth factor-β)cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory,pathogenic,and immune regulatory.How TGF-β superfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two decades.Here,we introduce the fundamental biology of TGF-β superfamily signaling,Treg cells,and Th17 cells and discuss in detail how the TGF-β superfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.
查看更多>>摘要：CD8+ T cells are the key executioners of the adaptive immune arm,which mediates antitumor and antiviral immunity.Naïve CD8+ T cells develop in the thymus and are quickly activated in the periphery after encountering a cognate antigen,which induces these cells to proliferate and differentiate into effector cells that fight the initial infection.Simultaneously,a fraction of these cells become long-lived memory CD8+ T cells that combat future infections.Notably,the generation and maintenance of memory cells is profoundly affected by various in vivo conditions,such as the mode of primary activation(e.g.,acute vs.chronic immunization)or fluctuations in host metabolic,inflammatory,or aging factors.Therefore,many T cells may be lost or become exhausted and no longer functional.Complicated intracellular signaling pathways,transcription factors,epigenetic modifications,and metabolic processes are involved in this process.Therefore,understanding the cellular and molecular basis for the generation and fate of memory and exhausted CD8+ cells is central for harnessing cellular immunity.In this review,we focus on mammalian target of rapamycin(mTOR),particularly signaling mediated by mTOR complex(mTORC)2 in memory and exhausted CD8+ T cells at the molecular level.
Eve PlayoustRomain RemarkEric VivierPierre Milpied...
1040-1050页
查看更多>>摘要：B cells play essential roles in immunity,mainly through the production of high affinity plasma cells(PCs)and memory B(Bmem)cells.The affinity maturation and differentiation of B cells rely on the integration of B-cell receptor(BCR)intrinsic and extrinsic signals provided by antigen binding and the microenvironment,respectively.In recent years,tumor infiltrating B(TIL-B)cells and PCs(TIL-PCs)have been revealed as important players in antitumor responses in human cancers,but their interplay and dynamics remain largely unknown.In lymphoid organs,B-cell responses involve both germinal center(GC)-dependent and GC-independent pathways for Bmem cell and PC production.Affinity maturation of BCR repertoires occurs in GC reactions with specific spatiotemporal dynamics of signal integration by B cells.In general,the reactivation of high-affinity Bmem cells by antigens triggers GC-independent production of large numbers of PC without BCR rediversification.Understanding B-cell dynamics in immune responses requires the integration of multiple tools and readouts such as single-cell phenotyping and RNA-seq,in situ analyses,BCR repertoire analysis,BCR specificity and affinity assays,and functional tests.Here,we review how those tools have recently been applied to study TIL-B cells and TIL-PC in different types of solid tumors.We assessed the published evidence for different models of TIL-B-cell dynamics involving GC-dependent or GC-independent local responses and the resulting production of antigen-specific PCs.Altogether,we highlight the need for more integrative B-cell immunology studies to rationally investigate TIL-B cells as a leverage for antitumor therapies.
查看更多>>摘要：The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid metabolism and inflammation.It is therefore not surprising that the list of human diseases associated with lymphatic malfunctions has grown larger,including issues beyond lymphedema,a pathology traditionally associated with lymphatic drainage insufficiency.Thus,the discovery of factors and pathways that can promote optimal lymphatic functions may offer new therapeutic options.Accumulating evidence indicates that aside from biochemical factors,biomechanical signals also regulate lymphatic vessel expansion and functions postnatally.Here,we review how mechanical forces induced by fluid shear stress affect the behavior and functions of lymphatic vessels and the mechanisms lymphatic vessels employ to sense and transduce these mechanical cues into biological signals.
查看更多>>摘要：Germinal centers(GCs)are essential for the establishment of long-lasting antibody responses.GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome.However,the critical proteins driving these key mechanisms are still unknown.Here,we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses.TIA1-and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection,expansion and differentiation into B-cell clones producing high-affinity antibodies.Mechanistically,TIA1 and TIAL1 control the transcriptional identity of dark-and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1.Thus,we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
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