Abstract:
:Decades of basic research has established the importance of Ca2+ to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca2+ influx and how this influx subsequently changes transcriptional activities in T cells. As chimeric antigen receptor (CAR)-T therapy has achieved great clinical success, is it possible to harness Ca2+ signaling to further advance CAR-T research? How is CAR signaling different from TCR signaling? How can functional CARs be identified in a high-throughput way? Quantification of various Ca2+ signals downstream of CAR/TCR activation might help answer these questions. Here we first summarized recent studies that used Ca2+ dye, genetically-encoded Ca2+ indicators (GECI) or transcriptional activity reporters to understand CAR activation in vitro and in vivo. We next reviewed several proof-of-concept reports that manipulate Ca2+ signaling by light or ultrasound to achieve precise spatiotemporal control of T cell functions. These efforts, though preliminary, opened up new avenues to solve the on-target/off-tumor problem of therapeutic T cells. Other modalities to regulate Ca2+ signaling, such as radio wave and electrical pulse, were also discussed. Thus, monitoring or manipulating Ca2+ signaling in T cells provides us many opportunities to advance cancer immunotherapy.
journal_name
Semin Immunoljournal_title
Seminars in immunologyauthors
Meng X,Wu X,Zheng Y,Shang K,Jing R,Jiao P,Zhou C,Zhou J,Sun Jdoi
10.1016/j.smim.2020.101434subject
Has Abstractpub_date
2020-06-01 00:00:00pages
101434eissn
1044-5323issn
1096-3618pii
S1044-5323(20)30050-6journal_volume
49pub_type
杂志文章,评审abstract::Immune receptors are coupled to the activation of phosphatidylcholine phospholipase D (PC-PLD) that hydrolyses phosphatidylcholine to generate phosphatidic acid and choline. As these receptors are also coupled to other signalling cascades, it has been difficult to define the precise cell activation events resulting fr...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.2001.0341
更新日期:2002-02-01 00:00:00
abstract::A humoral immune response in the form of autoantibodies to tumor antigens occurs early during tumor development. Identification of antigens that induce an autoantibody response restricted to a cancer type has the potential to yield markers useful for early detection. A multitude of strategies are currently available f...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2020.101388
更新日期:2020-02-01 00:00:00
abstract::Viral and microbial pathogens contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). RNA virus infection is also detected through TLR-independent mechanisms. Early viral replicative intermediates are detected by...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2009.05.001
更新日期:2009-08-01 00:00:00
abstract::A growing amount of evidences indicates that inflammaging - the chronic, low grade inflammation state characteristic of the elderly - is the result of genetic as well as environmental or stochastic factors. Some of these, such as the accumulation of senescent cells that are persistent during aging or accompany its pro...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2018.10.009
更新日期:2018-12-01 00:00:00
abstract::T helper (TH) cells can assume different phenotypes characterized by the secretion of distinct effector molecules. Interferon-gamma producing TH1 and IL-4 producing TH2 cells have long been recognized as important mediators of host defense, whereas regulatory T cells are known to suppress T cell responses. Recently, T...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2007.10.016
更新日期:2007-12-01 00:00:00
abstract::Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonar...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2014.09.003
更新日期:2014-12-01 00:00:00
abstract::The recombination activating genes 1 and 2 (Rag1 and Rag2) encode the key enzyme that is required for the generation of the highly diversified antigen receptor repertoire central to adaptive immunity. The longstanding model proposed that this gene pair was acquired by horizontal gene transfer to explain its abrupt app...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2009.11.004
更新日期:2010-02-01 00:00:00
abstract::Studies on oral immunotherapy (OIT) have been increasing worldwide. Nevertheless, some concerns exist with this treatment. The rate of long-term sustained unresponsiveness is quite low; moreover, the desensitization or sustained unresponsiveness does not equate to tolerance. Furthermore, adverse reactions are frequent...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2017.07.008
更新日期:2017-04-01 00:00:00
abstract::Interferon epsilon (IFNε) is a type I IFN with unusual patterns of expression and therefore, function. It is constitutively expressed by reproductive tract epithelium and regulated by hormones during estrus cycle, reproduction, and menopause and by exogenous hormones. The IFNe protein is encoded by a gene in the type ...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2019.101328
更新日期:2019-06-01 00:00:00
abstract::This review focuses on recessive mutations at three loci whose gene products play critical roles in the development and regulation of the murine immune system. These mutations are: severe combined immunodeficiency (scid), osteopetrosis (op), and motheaten (me). The scid mutation blocks differentiation of functional T ...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:
更新日期:1991-11-01 00:00:00
abstract::Many immune cells can detect the direction and intensity of an extracellular chemical gradient, and migrate toward the source of stimulus. This process, called chemotaxis, is essential for immune system function and homeostasis, and its deregulation is associated with serious diseases. Chemotaxis is initiated by chemo...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2004.09.005
更新日期:2005-02-01 00:00:00
abstract::As a component of all living cells and microbes, it is not surprising that organisms have evolved mechanisms to detect foreign or aberrant DNA and trigger an innate immune response. TLR9 is an endosomal membrane bound receptor that is widely studied and the best understood DNA sensor. However, the existence of TLR9-in...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2009.05.006
更新日期:2009-08-01 00:00:00
abstract::The humoral arm of the immune system provides robust protection against extracellular pathogens via the production of antibody molecules that neutralize or facilitate the destruction of microorganisms. However, the humoral immune system also provides a significant barrier to solid organ transplantation due to the anti...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2011.08.021
更新日期:2011-08-01 00:00:00
abstract::It is becoming increasingly accepted that macrophages play a crucial role in many diseases associated with chronic inflammation, including atherosclerosis, obesity, diabetes, cancer, skin diseases, and even neurodegenerative diseases. It is therefore not surprising that macrophages in human diseases have gained signif...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2015.07.003
更新日期:2015-08-01 00:00:00
abstract::Alarmins are preformed, endogenous molecules that can be promptly released to signal cell or tissue stress or damage. The ubiquitous nuclear molecule high-mobility group box 1 protein (HMGB1) is a prototypical alarmin activating innate immunity. HMGB1 serves a dual alarmin function. The protein can be emitted to alert...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2018.02.011
更新日期:2018-08-01 00:00:00
abstract::The commensal microbiome constitutes an important modulator of host physiology and risk of disease, including cancer development and progression. Lately, the microbiome has been suggested to modulate the efficacy of anti-cancer treatment. Examples include chemotherapy and total body irradiation-induced barrier functio...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2017.04.001
更新日期:2017-08-01 00:00:00
abstract::The ability of the immune system to discriminate between healthy-self, abnormal-self, and non-self has been attributed mainly to alarmins signaling as "danger signals". It is now evident, however, that alarmins are much more complex and can perform specialized functions that can regulate a wide spectrum of processes r...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2018.08.004
更新日期:2018-08-01 00:00:00
abstract::The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. ...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.1998.0146
更新日期:1998-12-01 00:00:00
abstract::Increasing interest in the initial steps of hemopoiesis in the embryo is prompted by the lack of information about the primordial origin and the nature of hemopoietic stem cells. It appears critical to understand the emergence, diversification and differentiation potential of hemopoietic cells in the preliver embryo. ...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/1044-5323(95)90041-1
更新日期:1995-06-01 00:00:00
abstract::Lymph nodes (LNs) represent the principal site where antigen-specific memory T- and B-cell responses are primed and differentiated into memory and effector cells. During chronic viral infections such as HIV, these lymphoid tissues undergo substantial structural changes. These changes are mostly caused by an imbalanced...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2008.07.008
更新日期:2008-06-01 00:00:00
abstract::It is now well established that the progression of T cell development requires interactions between the surfaces of thymocytes and thymic stromal cells. For example, the maturation of CD4+8+ cells into functional CD4+ or CD8+ cells requires TCR/MHC interactions, which, depending on the specificity of the particular TC...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.1994.1028
更新日期:1994-08-01 00:00:00
abstract::Leukocyte subsets are recruited from the blood to lymphoid and non-lymphoid tissues via a multi-step process that involves distinct adhesive and activation steps. Chemokines, a family of chemotactic cytokines that signal through G-protein-coupled receptors, play critical roles in regulating the leukocyte recruitment c...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.2001.0345
更新日期:2002-04-01 00:00:00
abstract::Antibody production is crucial for a successful vaccine response. Beyond the ability of vitamin A (VA) and its active metabolite, all-trans-retinoic acid (RA) to restore growth in VA-deficient animals, supplementation with VA and/or treatment with RA can augment antibody responses in both VA-deficient and VA-adequate ...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2008.08.004
更新日期:2009-02-01 00:00:00
abstract::Natural killer (NK) cells have traditionally been classified as a cellular component of the innate immune system, given their ability to rapidly produce effector cytokines and kill infected or transformed cells without prior exposure. More recently, NK cells have been shown to possess features of adaptive immunity suc...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2017.08.012
更新日期:2017-06-01 00:00:00
abstract::Monoclonal antibodies (MAb) specific for lymphocyte markers can be considered as very specific immunomodulating drugs for treatment of allograft rejection and autoimmune diseases. Although the selection of potentially useful specificities of MAb can be made in rodents, human specific MAb can only be evaluated in man o...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:
更新日期:1990-11-01 00:00:00
abstract::V(D)J recombination consists of a DNA cleavage reaction catalysed by RAG1 and RAG2, followed by an end-joining reaction that utilizes the cell's double-strand break repair machinery. Genes essential for the end-joining reaction include: XRCC4 encoding a protein of unknown enzymatic function; XRCC5 and XRCC6 encoding 8...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.1997.0070
更新日期:1997-06-01 00:00:00
abstract::Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typic...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2017.04.004
更新日期:2017-02-01 00:00:00
abstract::Recent evidence indicates that memory B cells may originate from a precursor cell subset that is distinct from AFC precursors. Most convincing is the finding that fractionation of naive peripheral B-cell populations on the basis of surface heat stable antigen (HSA) expression yields two populations; one greatly enrich...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.1997.0075
更新日期:1997-08-01 00:00:00
abstract::The acute retroviral syndrome associated with primary HIV-1 infection is characterized by clinical signs of immune activation, multi-system dysfunction, and high levels of cell-associated and plasma viremia, p24 antigenemia, and proviral burden. Clinical abnormalities associated with acute HIV-1 infection and measures...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1006/smim.1993.1018
更新日期:1993-06-01 00:00:00
abstract::Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in cellular metabolism are important determinants of macrophage function and phenotype. At the same time, our appreciation of macrophage diversity in vivo has a...
journal_title:Seminars in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.smim.2016.10.004
更新日期:2016-10-01 00:00:00