Abstract：
:Glyco-immune checkpoint receptors, molecules that inhibit immune cell activity following binding to glycosylated cell-surface antigens, are emerging as attractive targets for cancer immunotherapy. Defining biologically relevant ligands that bind and activate such receptors, however, has historically been a significant challenge. Here, we present a CRISPRi genomic screening strategy that allowed unbiased identification of the key genes required for cell-surface presentation of glycan ligands on leukemia cells that bind the glyco-immune checkpoint receptors Siglec-7 and Siglec-9. This approach revealed a selective interaction between Siglec-7 and the mucin-type glycoprotein CD43. Further work identified a specific N-terminal glycopeptide region of CD43 containing clusters of disialylated O-glycan tetrasaccharides that form specific Siglec-7 binding motifs. Knockout or blockade of CD43 in leukemia cells relieves Siglec-7-mediated inhibition of immune killing activity. This work identifies a potential target for immune checkpoint blockade therapy and represents a generalizable approach to dissection of glycan-receptor interactions in living cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Wisnovsky S,Möckl L,Malaker SA,Pedram K,Hess GT,Riley NM,Gray MA,Smith BAH,Bassik MC,Moerner WE,Bertozzi CRdoi
10.1073/pnas.2015024118subject
Has Abstractpub_date
2021-02-02 00:00:00issue
5eissn
0027-8424issn
1091-6490pii
2015024118journal_volume
118pub_type
杂志文章abstract：:A paradigm of evolutionary biology is that adaptation and reproductive isolation are caused by a nearly infinite number of mutations of individually small effect. Here, we test this hypothesis by investigating the genetic basis of pollinator discrimination in two closely related species of monkeyflowers that differ in...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.96.21.11910
更新日期：1999-10-12 00:00:00
abstract：:We have investigated whether the large (5- to 15-fold) stimulation of synthesis of growth hormone (somatotropin) observed upon exposure of a strain of rat pituitary (GH3) cells to dexamethasone (a synthetic glucocorticoid) arises from a stimulation of pregrowth hormone mRNA. A good agreement was observed between the s...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.74.6.2357
更新日期：1977-06-01 00:00:00
abstract：:Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against co...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0603420103
更新日期：2007-01-02 00:00:00
abstract：:Although the F-specific ssRNA phage MS2 has long had paradigm status, little is known about penetration of the genomic RNA (gRNA) into the cell. The phage initially binds to the F-pilus using its maturation protein (Mat), and then the Mat-bound gRNA is released from the viral capsid and somehow crosses the bacterial e...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.2011901117
更新日期：2020-10-13 00:00:00
abstract：:The engineering of structures across different length scales is central to the design of novel materials with controlled macroscopic properties. Herein, we introduce a unique class of self-assembling materials, which are built upon shape- and volume-persistent molecular nanoparticles and other structural motifs, such ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1302606110
更新日期：2013-06-18 00:00:00
abstract：:Metastasis of solid tumors is a key determinant of cancer patient survival. Targeting micrometastases using nanoparticles could offer a way to stop metastatic tumor growth before it causes excessive patient morbidity. However, nanoparticle delivery to micrometastases is difficult to investigate because micrometastases...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2017-03-21 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0500803102
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2015-02-03 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
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更新日期：2009-05-05 00:00:00
abstract：:We isolated mutant strains of the facultative anaerobe Salmonella typhimurium that grow either aerobically or anaerobically. Strict anaerobic mutants contained a defective DNA topoisomerase I gene (topI), while strict aerobic mutants contained a defective DNA gyrase subunit A gene (gyrA, also nalA). Topoisomerase I ac...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.82.7.2077
更新日期：1985-04-01 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1811465115
更新日期：2018-12-26 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1606791113
更新日期：2016-10-18 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
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更新日期：2009-04-14 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2016-02-23 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0501104102
更新日期：2005-05-31 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.050316997
更新日期：2000-02-29 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2007-12-18 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2011-02-01 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
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更新日期：1981-07-01 00:00:00
abstract：:The classic anthropological hypothesis known as the "obstetrical dilemma" is a well-known explanation for human altriciality, a condition that has significant implications for human social and behavioral evolution. The hypothesis holds that antagonistic selection for a large neonatal brain and a narrow, bipedal-adapte...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2012-09-18 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2018-11-06 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.87.19.7433
更新日期：1990-10-01 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.2002918117
更新日期：2020-07-21 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2011-01-25 00:00:00
abstract：:The lentiviruses are associated with a wide range of chronic diseases in mammals. These include immunodeficiencies (such as HIV/AIDS in humans), malignancies, and lymphatic and neurological disorders in primates, felids, and a variety of wild and domesticated ungulates. Evolutionary analyses of the genomic sequences o...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
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abstract：:Inelastic electron tunneling spectra of nucleosides and nucleotides are presented which show that detailed information on the vibrational spectra of these molecules can be obtained from a few micrograms of material. A series of studies on adenine derivatives demonstrates that unambiguous identification of a large numb...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.73.5.1598
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abstract：:Significantly above-chance detection of stimuli presented within the field defect of patients with postgeniculate lesions is termed "blindsight." It has been proposed that those with blindsight are more likely to benefit from visual rehabilitation by repeated stimulation, leading to increased visual sensitivity within...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1318395110
更新日期：2013-11-05 00:00:00
abstract：:Humans speak, monkeys grunt, and ducks quack. How do we come to know which vocalizations animals produce? Here we explore this question by asking whether young infants expect humans, but not other animals, to produce speech, and further, whether infants have similarly restricted expectations about the sources of vocal...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0906049106
更新日期：2009-11-03 00:00:00
