Abstract:
:Inciting the cellular arm of adaptive immunity has been the fundamental goal of cancer immunotherapy strategies, specifically focusing on inducing tumor antigen-specific responses by CD8(+) cytotoxic T lymphocytes (CTL). However, there is an emerging appreciation that the cytotoxic function of CD4(+) T cells can be effective in a clinical setting. Harnessing this potential will require an understanding of how such cells arise. In this study, we use an IL12-transduced variant of the 70Z/3 leukemia cell line in a B6D2F1 (BDF1) murine model system to reveal a novel cascade of cells and soluble factors that activate anticancer CD4(+) killer cells. We show that natural killer T cells play a pivotal role by activating dendritic cells in a contact-dependent manner; soluble products of this interaction, including MCP-1, propagate the activation signal, culminating in the development of CD4(+) CTLs that directly mediate an antileukemia response while also orchestrating a multipronged attack by other effector cells. A more complete picture of the conditions that induce such a robust response will allow us to capitalize on CD4(+) T-cell plasticity for maximum therapeutic effect.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Nelles ME,Moreau JM,Furlonger CL,Berger A,Medin JA,Paige CJdoi
10.1158/2326-6066.CIR-13-0208subject
Has Abstractpub_date
2014-11-01 00:00:00pages
1113-24issue
11eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-13-0208journal_volume
2pub_type
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abstract::Ligand-receptor complexes play a central role in mediating a range of processes in immunology and cancer biology. The ability to directly quantify the fraction of receptors occupied by a ligand in a given biospecimen, as opposed to assessing the concentration of ligand and receptor separately, could provide an additio...
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journal_title:Cancer immunology research
pub_type:
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journal_title:Cancer immunology research
pub_type: 杂志文章,评审
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journal_title:Cancer immunology research
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更新日期:2014-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0114
更新日期:2015-04-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 杂志文章,多中心研究
doi:10.1158/2326-6066.CIR-17-0475
更新日期:2018-07-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0200-T
更新日期:2016-03-01 00:00:00
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doi:10.1158/2326-6066.CIR-18-0605
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journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0082
更新日期:2020-08-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0156
更新日期:2016-12-01 00:00:00
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
pub_type: 杂志文章
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更新日期:2014-03-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0309
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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更新日期:2015-05-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 临床试验,杂志文章
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更新日期:2014-02-01 00:00:00
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journal_title:Cancer immunology research
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doi:10.1158/2326-6066.CIR-13-0001
更新日期:2013-09-01 00:00:00
abstract::Despite the rapid progress in the development of novel adoptive T-cell therapies, the clinical benefits in treatment of established tumors have remained modest. Several immune evasion mechanisms hinder T-cell entry into tumors and their activity within the tumor. Of note, oncolytic adenoviruses are intrinsically immun...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0220-T
更新日期:2015-08-01 00:00:00
abstract::Many immunotherapeutic approaches under development rely on T-cell recognition of cancer-derived peptides bound to human leukocyte antigen molecules on the cell surface. Direct experimental demonstration that such peptides are processed and bound is currently challenging. Here, we describe a method that meets this cha...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0107
更新日期:2019-11-01 00:00:00