Abstract：
:The full potential of T cell-based immunotherapies remains limited by a variety of T cell extrinsic and intrinsic immunosuppressive mechanisms that can become imprinted to stably reduce the antitumor ability of T cells. Here, we discuss recent insights into memory CD8+ T cell differentiation and exhaustion and the association of these differentiation states with clinical outcomes during immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapeutic modalities. We consider the barriers limiting immunotherapy with a focus on epigenetic regulation impeding efficacy of adoptively transferred T cells and other approaches that augment T cell responses such as immune checkpoint blockade. Furthermore, we outline conceptual and technical breakthroughs that can be applied to existing therapeutic approaches and to the development of novel cutting-edge strategies.
journal_name
Trends Immunoljournal_title
Trends in immunologyauthors
Zebley CC,Gottschalk S,Youngblood Bdoi
10.1016/j.it.2020.06.008subject
Has Abstractpub_date
2020-08-01 00:00:00pages
665-675issue
8eissn
1471-4906issn
1471-4981pii
S1471-4906(20)30132-0journal_volume
41pub_type
杂志文章,评审abstract：:Macrophages mount complex responses to pathogens. Although several key signaling pathways have been identified, it remains unclear how they work together to provide specificity. In a recent paper, Gottschalk et al. report that differential dose-response behaviors of the NFκB and MAPK pathways allow dose-specific gene ...
journal_title：Trends in immunology
pub_type： 评论,杂志文章
doi：10.1016/j.it.2016.07.003
更新日期：2016-09-01 00:00:00
abstract：:Monoclonal antibodies (mAbs) are in widespread use for the treatment of cancer. Their success as cancer therapeutics relies substantially on their ability to engage the immune system. Specifically, Fc-receptor-expressing immune cells mediate the killing of tumor cells by mAbs. Stimulation of these immune effector cell...
journal_title：Trends in immunology
pub_type： 杂志文章
doi：10.1016/j.it.2011.07.003
更新日期：2011-11-01 00:00:00
abstract：:Migration of hematopoietic stem cells (HSCs) is essential during embryonic development and throughout adult life. During embryogenesis, trafficking of HSCs is responsible for the sequential colonization of different hematopoietic organs by blood-producing cells. In adulthood, circulation of HSCs maintains homeostasis ...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2011.06.011
更新日期：2011-10-01 00:00:00
abstract：:House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2011.06.006
更新日期：2011-09-01 00:00:00
abstract：:Cell migration is crucial for intrathymic T-cell differentiation. Chemokines and extracellular matrix proteins per se induce thymocyte migration, and recent data suggest a combinatorial role for these molecules in this event. For example, thymocyte migration induced by fibronectin plus CXCL12/SDF1-alpha (stromal cell-...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4906(02)02224-x
更新日期：2002-06-01 00:00:00
abstract：:CD8+ T cell immunological memory of past antigen exposure can confer long-lived protection against infections or tumors. The fact that CD8+ memory T cells can have features of both naïve and effector cells has forced the field to struggle with several conceptual questions about the developmental origin of the cell and...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2019.11.004
更新日期：2020-01-01 00:00:00
abstract：:T follicular helper (TFH) cells are characteristically defined by their CXCR5 positivity and homing to B cell follicles in secondary lymphoid organs (SLO). An expanded subpopulation of functionally comparable and phenotypically similar PD-1hiCXCR5-CD4+ T cells were recently identified in breast cancer (BC) and rheumat...
journal_title：Trends in immunology
pub_type： 杂志文章
doi：10.1016/j.it.2017.10.003
更新日期：2017-12-01 00:00:00
abstract：:NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitog...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2017.01.001
更新日期：2017-04-01 00:00:00
abstract：:Recent studies have reported paradoxical roles of inflammation in tumor immunity triggered by PD-1 checkpoint antibody (Ab) blockade. Here, we elaborate on this controversy and propose a new perspective that might help understand this paradox. Since inflammatory cytokines and PD-1 blockade are known to target differen...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2020.09.003
更新日期：2020-11-01 00:00:00
abstract：:In addition to exogenous ligands derived from pathogens, natural killer (NK) and other innate cells can recognize endogenous ligands that often act as markers of stress or damage. A recent study reports that one of these receptors, human NKp44, recognizes PDGF-DD, providing a rare example of the recognition of a solub...
journal_title：Trends in immunology
pub_type： 评论,杂志文章
doi：10.1016/j.it.2018.02.002
更新日期：2018-05-01 00:00:00
abstract：:Epstein-Barr Virus (EBV) is one of the most successful human viruses, infecting more than 90% of the adult population worldwide and persisting for the lifetime of the host. Individuals with a history of symptomatic primary EBV infection, called infectious mononucleosis, carry a moderately higher risk of developing mul...
journal_title：Trends in immunology
pub_type： 杂志文章
doi：10.1016/j.it.2009.03.007
更新日期：2009-06-01 00:00:00
abstract：:Although therapy-mediated suppression of HIV-1 is effective and results in a degree of immune reconstitution, the complications resulting from life-long treatment emphasize the need for alternatives. This review discusses the use of structured interruptions in antiviral therapy to induce drug-free periods of immune-me...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4906(00)01809-3
更新日期：2001-02-01 00:00:00
abstract：:Immune suppression by T(reg) cells must be overcome to mount robust and effective anti-pathogen immune responses. A new paper in Immunity from Medzhitov and colleagues shows that IL-1-dependent activation of MyD88 promotes the development of Th1 cells by rendering them impervious to T(reg) cell-mediated inhibition. ...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2014.02.001
更新日期：2014-03-01 00:00:00
abstract：:The introduction of combined antiretroviral therapies (HAART) has reversed the fatal course of human immunodeficiency virus (HIV) infection. HAART controls virus production and, in most cases, allows the quantitative and functional immune defects caused by HIV to be reversed. Here, we review T cell homeostatic mechani...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2010.12.002
更新日期：2011-03-01 00:00:00
abstract：:Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic imm...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2016.11.008
更新日期：2017-03-01 00:00:00
abstract：:Manipulating the immune system in order to induce clinically relevant responses against cancer is a longstanding goal. Interventions to enhance tumor-specific immunity through vaccination, sustaining effector T cell activation, or increasing the numbers of tumor-specific T cells using ex vivo expansion, have all resul...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2012.08.004
更新日期：2013-02-01 00:00:00
abstract：:CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine phosphatase. Many isoforms are generated by alternative splicing, but their function remains obscure. The extracellular domain of CD45 is highly polymorphic in all vertebrates. Importantly, human polymorphic variants that alter CD45 isoform e...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2006.01.001
更新日期：2006-03-01 00:00:00
abstract：:Inducing sustained, robust CD8(+) T cell responses is necessary for therapeutic intervention in chronic infectious diseases and cancer. Unfortunately, most adjuvant formulations fail to induce substantial cellular immunity in humans. Attenuated acute infectious agents induce strong CD8(+) T cell immunity, and are thou...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2016.01.001
更新日期：2016-03-01 00:00:00
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journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2008.07.004
更新日期：2008-10-01 00:00:00
abstract：:In lymphatic tissue, professional antigen-presenting cells (APCs) such as dendritic cells (DCs), mature after sensing microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs), and subsequently activate T cell immunity. Non-pathogenic MAMPs, derived for example from commensal bacteria, are ...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2010.06.001
更新日期：2010-08-01 00:00:00
abstract：:When and how adaptive immunity emerged is one of the fundamental questions in immunology. Accumulated evidence suggests that the key components of adaptive immunity, rearranging receptor genes and the MHC, are unique to jawed vertebrates. Recent studies in protochordates, in particular, the draft genome sequence of th...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2003.11.005
更新日期：2004-02-01 00:00:00
abstract：:Glioblastoma is an aggressive and incurable primary brain tumor. While the blockade of immune checkpoints leads to reversal of T cell exhaustion in many cancers, the efficacy of this therapy in glioblastoma requires further consideration of the brain microenvironment beyond T cell activity. Neural cells are crucially ...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2016.11.005
更新日期：2017-02-01 00:00:00
abstract：:T cell metabolism has a central role in supporting and shaping immune responses and may have a key role in antitumor immunity. T cell metabolism is normally held under tight regulation in an immune response of glycolysis to promote effector T cell expansion and function. However, tumors may deplete nutrients, generate...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2015.02.007
更新日期：2015-04-01 00:00:00
abstract：:Helminth parasites survive through a combination of parasite longevity, repeated re-infection and selective immune suppression to prevent protective Th2 responses. To counteract helminth-induced immunosuppression, and to induce long-term immunological memory, understanding of the multiple regulatory pathways within th...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2012.01.001
更新日期：2012-04-01 00:00:00
abstract：:The innate immune system is the first line of defense against invading pathogens and is particularly important in warding off bacterial and viral infections presenting at the mucosal cell surface. From this primitive immune response, the more sophisticated adaptive immune system was derived. Despite nearly two decades...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4906(01)01925-1
更新日期：2001-06-01 00:00:00
abstract：:Autophagy is a group of cellular pathways that deliver cytoplasmic constituents for lysosomal degradation. The peptides generated from these pathways can be presented by MHC II molecules, making autophagy an important source of antigens for CD4+ T cells. In addition, modules of the molecular machinery of autophagy wer...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2016.08.017
更新日期：2016-11-01 00:00:00
abstract：:Inflammatory bowel diseases (IBDs) are chronic debilitating conditions, which impair the patient's quality of life significantly. Among them, Crohn's disease and ulcerative colitis are idiopathic disorders for which an infective etiology has long been sought. Here, we present an opinion in support of the hypothesis th...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4906(01)02000-2
更新日期：2001-09-01 00:00:00
abstract：:Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the p...
journal_title：Trends in immunology
pub_type： 杂志文章
doi：10.1016/j.it.2010.05.002
更新日期：2010-07-01 00:00:00
abstract：:How allergens trigger the T helper 2 (Th2) response that characterizes allergic lung inflammation is not well understood. Epithelium-derived alarmins released after an allergen encounter activate the innate immune system, including group 2 innate lymphoid cells (ILC2s) which produce the type 2 interleukins IL-5 and IL...
journal_title：Trends in immunology
pub_type： 杂志文章,评审
doi：10.1016/j.it.2015.01.005
更新日期：2015-03-01 00:00:00
abstract：:Natural killer (NK)-cell receptors (NKRs) on CD8+ T cells can modulate antigen-specific T-cell activity but their function and rules that govern their expression remain unclear. Recent work has provided new insight into CD94-NKG2A expression on T cells. Whereas upregulation on the cell surface is induced following T-c...
journal_title：Trends in immunology
pub_type： 杂志文章
doi：10.1016/s1471-4906(03)00064-4
更新日期：2003-04-01 00:00:00
