Abstract:
:The tumor microenvironment is characterized by of high levels of extracellular nucleotides that are metabolized through the dynamic and sequential action of cell surface enzymes (ectoenzymes). These ectoenzymes operate according to their spatial arrangement, as part of (1) continuous (molecules on the same cell) or (2) discontinuous (molecules on different cells) pathways, the latter being facilitated by restricted cellular microenvironment. The outcome of this catabolic activity is an increase in the local concentration of adenosine, a nucleoside involved in the control of inflammation and immune responses. The aim of the work presented here was to demonstrate that a previously unexplored enzymatic pathway may be an alternate route to produce extracellular adenosine. Our data show that this new axis is driven by the nucleotide-metabolizing ectoenzymes CD38 (an NAD+ nucleosidase), the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, also known as CD203a or PC-1) and the 5' ectonucleotidase (5'-NT) CD73, while bypassing the canonical catabolic pathway mediated by the nucleoside tri- and diphosphohydrolase (NTPDase) CD39. To determine the relative contributions of these cell surface enzymes to the production of adenosine, we exploited a human T-cell model allowing for the modular expression of the individual components of this alternative pathway upon activation and transfection. The biochemical analysis of the products of these ectoenzymes by high-performance liquid chromatography (HPLC) fully substantiated our working hypothesis. This newly characterized pathway may facilitate the emergence of an adaptive immune response in selected cellular contexts. Considering the role for extracellular adenosine in the regulation of inflammation and immunogenicity, this pathway could constitute a novel strategy of tumor evasion, implying that these enzymes may represent ideal targets for antibody-mediated therapy.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Horenstein AL,Chillemi A,Zaccarello G,Bruzzone S,Quarona V,Zito A,Serra S,Malavasi Fdoi
10.4161/onci.26246subject
Has Abstractpub_date
2013-09-01 00:00:00pages
e26246issue
9eissn
2162-4011issn
2162-402Xpii
2013ONCOIMM0216Rjournal_volume
2pub_type
杂志文章相关文献
OncoImmunology文献大全abstract::NY-ESO-1 (CTAG 1B) is highly expressed in the majority of synovial sarcomas and myxoid/round cell liposarcomas as well as in a subset of melanomas, but only rarely in other mesenchymal tumors. This points to a potential for using NY-ESO-1 in the differential diagnosis of these lesions. Furthermore, promising results h...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.21059
更新日期:2012-11-01 00:00:00
abstract::Interleukin-12 immune stimulation lacks efficacy in established solid tumor models. Disruption of tumor microenvironment homeostasis by low-dose cyclophosphamide prior to interleukin-12 gene therapy led to CD8+ T cell-driven established tumor rejection. This only takes place when inflammatory myeloid cells infiltrate ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.1.1.18049
更新日期:2012-01-01 00:00:00
abstract::Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a+ DCs found in the human skin to CD14+CD141+ macrophage-like cells. Here, as a...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.23837
更新日期:2013-04-01 00:00:00
abstract::Five-year survival rates for patients diagnosed with metastatic melanoma are less than 5%. Adoptive cell transfer (ACT) has achieved an objective response of 50% by Response Evaluation Criteria in Solid Tumors (RECIST) in this patient population. For ACT to be maximally effective, the host must first be lymphodepleted...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1019196
更新日期:2015-04-01 00:00:00
abstract::Natural killer (NK) cells are integral components of the antitumor immune response. The downregulation of ligands for NK-cell stimulatory receptors represents a strategy whereby glioblastoma cells can evade NK-cell attacks. Histone deacetylase inhibitors can stimulate the (re)expression of these ligands, driving cytot...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.25219
更新日期:2013-08-01 00:00:00
abstract::The advent of immune checkpoint blockade as a new strategy for immunotherapy has changed the outlook for many aggressive cancers. Although complete tumor eradication is attainable in some cases, durable clinical responses are observed only in a small fraction of patients, underlining urgent need for improvement. We pr...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1480286
更新日期:2018-07-11 00:00:00
abstract::Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broa...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1847846
更新日期:2020-11-19 00:00:00
abstract::CD69 is an early activation marker on the surface of T lymphocytes undergoing activation by cognate antigen. We observed intense expression of CD69 on tumor-infiltrating T-lymphocytes that reside in the hypoxic tumor microenvironment and hypothesized that CD69 could be, at least partially, under the control of the tra...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1283468
更新日期:2017-01-19 00:00:00
abstract::Efficient immunotherapy relies on the rapid generation of elevated amounts of cancer-specific T lymphocytes. We have recently demonstrated that both rapid and potent tumor-targeting immune responses can be induced with a heterologous prime-boost regimen consisting of poly-lactic co-glycolic acid (PLGA) microsphere-bas...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.27873
更新日期:2014-02-14 00:00:00
abstract::Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1085148
更新日期:2015-08-31 00:00:00
abstract::A substantial obstacle to the success of adoptive T cell-based cancer immunotherapy is the sub-optimal affinity of T-cell receptors (TCRs) for most tumor antigens. Genetically engineered TCRs that have enhanced affinity for specific tumor peptide-MHC complexes may overcome this barrier. However, this enhancement risks...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1682381
更新日期:2019-11-24 00:00:00
abstract::Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1423182
更新日期:2018-02-13 00:00:00
abstract::Despite increasing evidence for a protective role of invariant (i) NKT cells in the control of graft-versus-host disease (GVHD), the mechanisms underpinning regulation of the allogeneic immune response in humans are not known. In this study, we evaluated the distinct effects of human in vitro expanded and flow-sorted ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1470735
更新日期:2018-08-23 00:00:00
abstract::Anticancer immunotherapies are highly desired. Conversely, unwanted inflammatory or immune responses contribute to oncogenesis, tumor progression, and cancer-related death. For non-immunogenic therapies to inhibit tumor growth, they must promote, not prevent, the activation of anticancer immune responses. Here, the ce...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.27091
更新日期:2013-12-01 00:00:00
abstract::Interleukin-10 (IL-10) is a potent immunomodulatory cytokine, whose cellular targets have not yet been precisely identified. Dendritic cell (DC)-specific IL-10 receptor knockout mice exhibit exaggerated T-cell reactivation in the skin, highlighting a key role of DCs in the maintenance of local immune homeostasis, beyo...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.23186
更新日期:2013-03-01 00:00:00
abstract::A missense mutation in RHOA encoding p.Gly17 Val has been reported to occur frequently in angioimmunoblastic T-cell lymphoma (AITL). Here, we describe a murine model which expresses the human RHOA mutant gene product in a T-cell specific manner and develops AITL-like symptoms. Most transgenic mice feature with latency...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1746553
更新日期:2020-05-13 00:00:00
abstract::Breast cancer is the most common form of cancer in women worldwide. Although the survival among breast cancer patients has improved, there is still a large group of patients with dismal prognosis. One of the most important prognostic factors for poor prognosis is lymph node metastasis. Increasing knowledge concerning ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1848067
更新日期:2020-11-22 00:00:00
abstract::We have developed a highly versatile platform for the systematic retrieval of T-cell receptors (TCRs) from single-antigen-reactive T cells and for characterization of their function and specificity. This approach enables rapid extraction of multiple TCRs from repertoires in individuals and not only broadens the divers...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1005523
更新日期:2015-03-19 00:00:00
abstract::The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demons...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1315488
更新日期:2017-04-20 00:00:00
abstract::Despite recent therapeutic progress, plasmablastic lymphoma (PBL), a distinct entity of high grade B cell lymphoma, is still an aggressive lymphoma with adverse prognosis. PBL commonly occurs in patients with HIV infection and PBL cells frequently express Epstein Barr virus (EBV) genome with type I latency. Occasional...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1486950
更新日期:2018-07-30 00:00:00
abstract::In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the effector immune response thereby permitting tumor development. Indeed, in mouse models, their depletion can promote the regression of tumors of various origins, including renal cell carcinoma when located subcutaneous (SC). In the presen...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/21624011.2014.963395
更新日期:2014-12-21 00:00:00
abstract::Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains ther...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1624128
更新日期:2019-06-06 00:00:00
abstract::We have previously shown that the development of a major histocompatibility complex class I (MHC-I)-deficient tumor was favored in protein kinase C-θ knockout (PKC-θ-/-) mice compared to that occurring in wild-type mice. This phenomenon was associated with scarce recruitment of natural killer (NK) cells to the tumor s...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/21624011.2014.948705
更新日期:2014-11-14 00:00:00
abstract::The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cell...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1196299
更新日期:2016-07-15 00:00:00
abstract::Granulysin is a protein present in the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, with cytolytic activity against microbes and tumors. Previous work demonstrated the therapeutic effect of intratumoral injection of recombinant granulysin using in vivo models of breast cancer and mult...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1641392
更新日期:2019-07-22 00:00:00
abstract::Renal cell carcinoma (RCC) is an immunogenic tumor, but uses several immune-suppressive mechanisms to shift the balance from tumor immune response toward tumor growth. Although RCC has traditionally been considered to be radiation resistant, recent evidence suggests that hypofractionated radiotherapy contributes to sy...
journal_title:Oncoimmunology
pub_type: 杂志文章,评审
doi:10.1080/2162402X.2015.1042198
更新日期:2015-05-27 00:00:00
abstract::Type I interferon (IFN) release by irradiated cancer cells is paramount for radiation therapy to elicit anticancer immunity. Our findings demonstrate that mitochondrial outer membrane permeabilization (MOMP) triggered by RT enables exposure of mitochondrial DNA to the cytosol, hence setting off CGAS-driven type I IFN ...
journal_title:Oncoimmunology
pub_type: 社论
doi:10.1080/2162402X.2020.1797292
更新日期:2020-07-22 00:00:00
abstract::Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil ph...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1080414
更新日期:2015-10-06 00:00:00
abstract::Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological toler...
journal_title:Oncoimmunology
pub_type: 评审
doi:10.4161/onci.25771
更新日期:2013-10-01 00:00:00
abstract::Immune adjuvants aimed at initiating or re-activating host immunity against poorly immunogenic cancers represent a potential tool for immunotherapy. By employing the natural killer T (NKT) cell agonist α-galactosylceramide in a whole tumor cell therapeutic vaccine approach, we have achieved potent suppression of estab...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.22615
更新日期:2013-01-01 00:00:00