Abstract:
:Infiltration of immune cells into the tumor microenvironment (TME) can regulate growth and survival of neoplastic cells, impacting tumorigenesis and tumor progression. Correlations between the number of effector immune cells present in a tumor and clinical outcomes in many human tumors, including breast, have been widely described. Current immunotherapies utilizing checkpoint inhibitors or co-stimulatory molecule agonists aim to activate effector immune cells. However, tumors often lack adequate effector cell numbers within the TME, resulting in suboptimal responses to these agents. Chemerin (RARRES2) is a leukocyte chemoattractant widely expressed in many tissues and is known to recruit innate leukocytes. CMKLR1 is a chemotactic cellular receptor for chemerin and is expressed on subsets of dendritic cells, NK cells, and macrophages. We have previously shown that chemerin acts as a tumor suppressive cytokine in mouse melanoma models by recruiting innate immune defenses into the TME. Chemerin/RARRES2 is down-regulated in many tumors, including breast, compared to normal tissue counterparts. Here, using a syngeneic orthotopic EMT6 breast carcinoma model, we show that forced overexpression of chemerin by tumor cells results in significant recruitment of NK cells and T cells within the TME. While chemerin secretion by EMT6 cells did not alter their phenotypic behavior in vitro, it did significantly suppress tumor growth in vivo. To define the cellular effectors required for this anti-tumor phenotype, we depleted NK cells or CD8+ T cells and found that either cell type is required for chemerin-dependent suppression of EMT6 tumor growth. Finally, we show significantly reduced levels of RARRES2 mRNA in human breast cancer samples compared to matched normal tissues. Thus, for the first time we have shown that increasing chemerin expression within the breast carcinoma TME can suppress growth by recruitment of NK and T cells, thereby supporting this approach as a promising immunotherapeutic strategy.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Pachynski RK,Wang P,Salazar N,Zheng Y,Nease L,Rosalez J,Leong WI,Virdi G,Rennier K,Shin WJ,Nguyen V,Butcher EC,Zabel BAdoi
10.3389/fimmu.2019.00983subject
Has Abstractpub_date
2019-05-08 00:00:00pages
983issn
1664-3224journal_volume
10pub_type
杂志文章abstract::A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein....
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01663
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00047
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abstract::Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expr...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02310
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00372
更新日期:2014-08-14 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01182
更新日期:2018-05-29 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01779
更新日期:2020-08-07 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.03064
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01102
更新日期:2019-05-31 00:00:00
abstract::B lymphocytes are important in secreting antibodies that protect against invading pathogens such as viruses, bacteria, parasites, and also in mediating pathogenesis of allergic diseases and autoimmunity. B lymphocytes develop in the bone marrow and contain heavy and light chains, which upon ligation form an immunoglob...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.595535
更新日期:2020-10-30 00:00:00
abstract::Piscirickettsia salmonis, an aggressive intracellular pathogen, is the etiological agent of salmonid rickettsial septicemia (SRS). This is a chronic multisystemic disease that generates high mortalities and large losses in Chilean salmon farming, threatening the sustainability of the salmon industry. Previous reports ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.544718
更新日期:2020-11-12 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00775
更新日期:2017-07-13 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00600
更新日期:2019-03-28 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00169
更新日期:2012-06-19 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00194
更新日期:2013-07-15 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2011.00081
更新日期:2011-12-26 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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doi:10.3389/fimmu.2019.02331
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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doi:10.3389/fimmu.2017.01647
更新日期:2017-12-04 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00919
更新日期:2019-04-26 00:00:00
abstract::Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage betw...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00839
更新日期:2020-05-27 00:00:00
abstract::Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02390
更新日期:2018-10-16 00:00:00
abstract::The mucosal immune system is constantly exposed to antigen, whether it be food antigen, commensal bacteria, or harmful antigen. It is essential that the mucosal immune system can distinguish between harmful and non-harmful antigens, and initiate an active immune response to clear the harmful antigens, while initiating...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00203
更新日期:2012-07-18 00:00:00
abstract::Coronary artery disease (CAD) as part of the cardiovascular diseases is a pathology caused by atherosclerosis, a chronic inflammatory disease of the vessel wall characterized by a massive invasion of lipids and inflammatory cells into the inner vessel layer (intima) leading to the formation of atherosclerotic lesions;...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00373
更新日期:2015-07-21 00:00:00
abstract::We have developed a therapeutic vaccine consisting of a mixture of lethally-irradiated allogeneic cutaneous melanoma cell lines with BCG and GM-CSF as adjuvants. The CSF-470 vaccine is currently being assayed in a Phase II-III trial against medium-dose IFN-α2b. All vaccinated patients immunized intradermally developed...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00144
更新日期:2015-03-30 00:00:00
abstract::The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental iden...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00212
更新日期:2019-02-13 00:00:00