CD69 is a direct HIF-1α target gene in hypoxia as a mechanism enhancing expression on tumor-infiltrating T lymphocytes.

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 transcriptional hypoxia response. In line with this, human and mouse CD3-stimulated lymphocytes cultured under hypoxia (1% O2) showed increased expression of CD69 at the protein and mRNA level. Consistent with these findings, mouse T lymphocytes that had recently undergone hypoxia in vivo, as denoted by pimonidazole staining, were more frequently CD69+ in the tumor and bone marrow hypoxic tissue compartments. We found evidence for HIF-1α involvement both when using T-lymphocytes from inducible HIF-1α-/- mice and when observing tumor-infiltrating T-lymphocytes in mice whose T cells are HIF-1α-/-. Direct pro-transcriptional activity of HIF-1α on a newly identified hypoxia response element (HRE) found in the human CD69 locus was demonstrated by ChIP experiments. These results uncover a connection between the HIF-1α oxygen-sensing pathway and CD69 immunobiology.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Labiano S,Meléndez-Rodríguez F,Palazón A,Teijeira Á,Garasa S,Etxeberria I,Aznar MÁ,Sánchez-Paulete AR,Azpilikueta A,Bolaños E,Molina C,de la Fuente H,Maiso P,Sánchez-Madrid F,de Landázuri MO,Aragonés J,Melero I

doi

10.1080/2162402X.2017.1283468

subject

Has Abstract

pub_date

2017-01-19 00:00:00

pages

e1283468

issue

4

eissn

2162-4011

issn

2162-402X

pii

1283468

journal_volume

6

pub_type

杂志文章
  • Sepsis inhibits tumor growth in mice with cancer through Toll-like receptor 4-associated enhanced Natural Killer cell activity.

    abstract::Sepsis-induced immune dysfunctions are likely to impact on malignant tumor growth. Sequential sepsis-then-cancer models of tumor transplantation in mice recovering from sepsis have shown that the post-septic immunosuppressive environment was able to promote tumor growth. We herein addressed the impact of sepsis on pre...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1641391

    authors: Vigneron C,Mirouse A,Merdji H,Rousseau C,Cousin C,Alby-Laurent F,Mira JP,Chiche JD,Llitjos JF,Pène F

    更新日期:2019-07-19 00:00:00

  • Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity.

    abstract::The prostaglandin (PG) synthetase cyclooxygenase 2 (Cox-2) promotes tumorigenesis, tumor progression, and metastasis in a variety of human cancer entities including pancreatic ductal adenocarcinoma (PDAC). In this study, we demonstrate that in PDAC cells such as Colo357 cells, enhanced Cox-2 expression and increased r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/2162402X.2014.988460

    authors: Gonnermann D,Oberg HH,Kellner C,Peipp M,Sebens S,Kabelitz D,Wesch D

    更新日期:2015-01-07 00:00:00

  • Blockade of the PD-1 pathway enhances the efficacy of adoptive cell therapy against cancer.

    abstract::The blockade of the PD-1 pathway can increase the production of interferon γ by tumor-specific T cells located within or in the proximity of the malignant lesion, thereby increasing the chemokine-dependent trafficking of immune effector cells. This can boost the efficacy of adoptive T-cell therapy to achieve superior ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.22691

    authors: Peng W,Lizée G,Hwu P

    更新日期:2013-02-01 00:00:00

  • Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy.

    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

    authors: Sanderson JP,Crowley DJ,Wiedermann GE,Quinn LL,Crossland KL,Tunbridge HM,Cornforth TV,Barnes CS,Ahmed T,Howe K,Saini M,Abbott RJ,Anderson VE,Tavano B,Maroto M,Gerry AB

    更新日期:2019-11-24 00:00:00

  • Dual therapeutic benefit of electroporation-mediated DNA vaccination in vivo: Enhanced gene transfer and adjuvant activity.

    abstract::DNA vaccination consists of administering an antigen-coding nucleotide sequence. In order to improve the efficacy of DNA vaccines, electroporation is one of the most commonly used methods to enhance DNA uptake. Here, we discuss additional immunological effects of electroporation that are key aspects for inducing immun...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28540

    authors: Calvet CY,André FM,Mir LM

    更新日期:2014-04-29 00:00:00

  • Tumor evasion of humoral immunity mediated by proteolytic impairment of antibody triggered immune effector function.

    abstract::Immune suppression is recognized as a hallmark of cancer and this notion is largely based on studies on cellular immunity. Our recent studies have demonstrated a potential new mechanism of cancer suppression of immunity by impairment of antibody effector function mediated by proteolytic enzymes in the tumor microenvir...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1122861

    authors: Zhang N,Jordan RE,An Z

    更新日期:2015-12-29 00:00:00

  • RhoGDI2 suppresses bladder cancer metastasis via reduction of inflammation in the tumor microenvironment.

    abstract::Low expression of RhoGDI2 is associated with poor outcome in cancer patients. In animal models, RhoGDI2 suppresses lung metastasis by reducing the expression of the proteoglycan versican, whose levels portend poor patient prognosis. Versican promotes metastasis through enhanced tumor migration and creation of an infla...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.20594

    authors: Said N,Theodorescu D

    更新日期:2012-10-01 00:00:00

  • Tumor-infiltrating podoplanin+ cells in gastric cancer: clinical outcomes and association with immune contexture.

    abstract::Podoplanin (PDPN) has been proved to have significant immunoregulatory effects in several types of malignancies and is considered to be a novel immune checkpoint molecule. However, the clinical significance of PDPN and its potential influence on immune contexture in gastric cancer remain obscure. Here, we aimed to inv...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1845038

    authors: Liu X,Cao Y,Lv K,Gu Y,Jin K,He X,Fang H,Fei Y,Shi M,Lin C,Liu H,Li H,He H,Xu J,Li R,Zhang H

    更新日期:2020-11-13 00:00:00

  • TLR2 ligation protects effector T cells from regulatory T-cell mediated suppression and repolarizes T helper responses following MVA-based cancer immunotherapy.

    abstract::Cancer immunotherapy is hampered by the immunosuppression maintained by regulatory T cells (Tregs) in tumor-bearing hosts. Stimulation of the Toll-like receptor 2 (TLR2) by Pam3Cys is known to affect Treg-mediated suppression. We found that Pam3Cys increases the proliferation of both CD4(+) effector T cells (Teffs) an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21479

    authors: Amiset L,Fend L,Gatard-Scheikl T,Rittner K,Duong V,Rooke R,Muller S,Bonnefoy JY,Préville X,Haegel H

    更新日期:2012-11-01 00:00:00

  • Strategies for purging CD96+ stem cells in vitro and in vivo: New avenues for autologous stem cell transplantation in acute myeloid leukemia.

    abstract::The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse. The selective elimination of CD96+ AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24500

    authors: Staudinger M,Humpe A,Gramatzki M

    更新日期:2013-06-01 00:00:00

  • A novel immunization strategy using cytokine/chemokines induces new effective systemic immune responses, and frequent complete regressions of human metastatic melanoma.

    abstract::Immune responses have been elicited by a variety of cancer vaccines, but seldom induce regressions of established cancers in humans. As a novel therapeutic immunization strategy, we tested the hypothesis that multiple cytokines/chemokines secreted early in secondary responses ex-vivo might mimic the secretory environm...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1386827

    authors: Valentine FT,Golomb FM,Harris M,Roses DF

    更新日期:2017-10-30 00:00:00

  • Invariant NKT cells: Killers and conspirators against cancer.

    abstract::Although invariant natural killer T (iNKT) cells influence antitumor responses indirectly by secreting cytokines and promoting the cytolytic functions of T and NK cells, we find that iNKT cells mediate direct tumoricidal activity in vitro and significantly inhibit tumor growth in vivo, even in the absence of other cyt...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27440

    authors: Bassiri H,Das R,Nichols KE

    更新日期:2013-12-01 00:00:00

  • Primary sterile necrotic cells fail to cross-prime CD8(+) T cells.

    abstract::Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns (DAMPs). However, how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions, in the absence of pathogen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21098

    authors: Gamrekelashvili J,Ormandy LA,Heimesaat MM,Kirschning CJ,Manns MP,Korangy F,Greten TF

    更新日期:2012-10-01 00:00:00

  • IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils.

    abstract::The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resul...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1317420

    authors: Lucarini V,Ziccheddu G,Macchia I,La Sorsa V,Peschiaroli F,Buccione C,Sistigu A,Sanchez M,Andreone S,D'Urso MT,Spada M,Macchia D,Afferni C,Mattei F,Schiavoni G

    更新日期:2017-04-20 00:00:00

  • Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma.

    abstract::Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment facto...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1507668

    authors: Moyes KW,Davis A,Hoglund V,Haberthur K,Lieberman NA,Kreuser SA,Deutsch GH,Franco S,Locke D,Carleton MO,Gilbertson DG,Simmons R,Winter C,Silber J,Gonzalez-Cuyar LF,Ellenbogen RG,Crane CA

    更新日期:2018-08-27 00:00:00

  • IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells.

    abstract::The functional status of CD4(+) T cells is a critical determinant of antitumor immunity. Polyfunctional CD4(+) T cells possess the ability to concomitantly produce multiple Th1-type cytokines, exhibiting a functional attribute desirable for cancer immunotherapy. However, the mechanisms by which these cells are induced...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1171445

    authors: Ding ZC,Liu C,Cao Y,Habtetsion T,Kuczma M,Pi W,Kong H,Cacan E,Greer SF,Cui Y,Blazar BR,Munn DH,Zhou G

    更新日期:2016-04-25 00:00:00

  • Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.

    abstract::The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1027469

    authors: Dai H,Zhang W,Li X,Han Q,Guo Y,Zhang Y,Wang Y,Wang C,Shi F,Zhang Y,Chen M,Feng K,Wang Q,Zhu H,Fu X,Li S,Han W

    更新日期:2015-05-26 00:00:00

  • Understanding anti-leukemia responses to donor lymphocyte infusion.

    abstract::Donor lymphocyte infusion (DLI) is an established and potentially curative immune therapy for relapsed leukemia after hematopoietic stem cell transplant (HSCT). Herein, we describe the utility of DLI as a tractable model system to glean fresh insights into understanding and predicting effective anti-leukemia immunity....

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28187

    authors: Bachireddy P,Wu CJ

    更新日期:2014-03-17 00:00:00

  • Th1 epitope selection for clinically effective cancer vaccines.

    abstract::New cancer immunotherapies mark progress in our understanding of tumor biology and harnessing the immune system's management of self. However, protein- and peptide-based vaccines are not yet consistently efficacious. Recent work uncovers principles governing the genesis of T helper type-restrictive immunity to self-an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.954971

    authors: Disis ML,Watt WC,Cecil DL

    更新日期:2014-12-13 00:00:00

  • TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer.

    abstract::Advanced ovarian cancer (OC) patients have a poor 5-year survival of only 28%, emphasizing the medical need for improved therapies. Adjuvant immunotherapy could be an attractive approach since OC is an immunogenic disease and the presence of tumor-infiltrating lymphocytes has shown to positively correlate with patient...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1843247

    authors: Maas RJ,Hoogstad-van Evert JS,Van der Meer JM,Mekers V,Rezaeifard S,Korman AJ,de Jonge PK,Cany J,Woestenenk R,Schaap NP,Massuger LF,Jansen JH,Hobo W,Dolstra H

    更新日期:2020-11-08 00:00:00

  • Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy.

    abstract::Checkpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1308616

    authors: Terabe M,Robertson FC,Clark K,De Ravin E,Bloom A,Venzon DJ,Kato S,Mirza A,Berzofsky JA

    更新日期:2017-03-31 00:00:00

  • Inhibition of formyl peptide receptor 1 reduces the efficacy of anticancer chemotherapy against carcinogen-induced breast cancer.

    abstract::The loss-of-function mutation of formyl peptide receptor 1 (FPR1) has a negative impact on the progression-free and overall survival of breast cancer patients treated with anthracycline-based adjuvant chemotherapy. This effect may be attributed to the fact that chemotherapy-induced antitumor immunity requires FPR1 and...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1139275

    authors: Baracco EE,Pietrocola F,Buqué A,Bloy N,Senovilla L,Zitvogel L,Vacchelli E,Kroemer G

    更新日期:2016-02-18 00:00:00

  • Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer.

    abstract::Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the express...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1274477

    authors: Dewi DL,Mohapatra SR,Blanco Cabañes S,Adam I,Somarribas Patterson LF,Berdel B,Kahloon M,Thürmann L,Loth S,Heilmann K,Weichenhan D,Mücke O,Heiland I,Wimberger P,Kuhlmann JD,Kellner KH,Schott S,Plass C,Platten M,Gerhä

    更新日期:2017-01-03 00:00:00

  • Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors.

    abstract::Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1655360

    authors: Kaffes I,Szulzewsky F,Chen Z,Herting CJ,Gabanic B,Velázquez Vega JE,Shelton J,Switchenko JM,Ross JL,McSwain LF,Huse JT,Westermark B,Nelander S,Forsberg-Nilsson K,Uhrbom L,Maturi NP,Cimino PJ,Holland EC,Kettenmann H,

    更新日期:2019-08-22 00:00:00

  • Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation.

    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

    authors: Lee GJ,Jun Y,Yoo HY,Jeon YK,Lee D,Lee S,Kim J

    更新日期:2020-05-13 00:00:00

  • Acute myeloid leukemia and NK cells: two warriors confront each other.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous disease whose therapies currently show elevated toxicity and a high rate of relapse. Recently, the burgeoning of new anti-tumor therapeutic strategies aimed at enhancing the immune response has pushed natural killer cells (NKs) into the spotlight. These cells are powerfu...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1539617

    authors: Baragaño Raneros A,López-Larrea C,Suárez-Álvarez B

    更新日期:2018-10-31 00:00:00

  • Enhanced 15-lipoxygenase activity and elevated eicosanoid production in kidney tumor microenvironment contribute to the inflammation and immune suppression.

    abstract::Macrophage infiltration is a hallmark in the majority of solid tumors. Our studies demonstrated that macrophages that infiltrate human renal cells carcinoma (RCC) display markedly enhanced expression and activity of 15-lipoxygenase-2 (15-LOX2). Obtained data suggest that enhanced lipoxygenase activity in tumor-associa...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.2.18502

    authors: Kusmartsev S

    更新日期:2012-03-01 00:00:00

  • Inhibition of CXCLs/CXCR2 axis in the tumor microenvironment might be a potent therapeutics for pancreatic cancer.

    abstract::Pancreatic cancer is characterized by expanded stroma with marked fibrosis. In Ijichi et al., we show that inhibiting CXCR2 disrupts tumor-stromal interactions and improves survival of a genetically-engineered mouse model recapitulating human pancreatic cancer. Targeting CXCLs/CXCR2 axis in the tumor microenvironment ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19402

    authors: Ijichi H

    更新日期:2012-07-01 00:00:00

  • Subverting the adaptive immune resistance mechanism to improve clinical responses to immune checkpoint blockade therapy.

    abstract::The correlation between tumor-infiltrating lymphocyte (TIL)-expression of programmed cell death ligand 1 (PD-L1) and clinical responsiveness to the PD-1 blocking antibody nivolumab implicates adaptive immune evasion mechanisms in cancer. We review our findings that tumor cell PD-L1 expression is induced by interferon ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.954868

    authors: Kim YJ

    更新日期:2015-01-07 00:00:00

  • The role of Type I interferons in immunoregulation of breast cancer metastasis to the bone.

    abstract::Breast cancer spread to distant sites is often incurable. Our recent findings demonstrate that Type I interferons secreted by tumor cells induce anti-metastatic immune responses that prevent breast cancer metastasis to the bone. This provides novel insights into the importance of the crosstalk between neoplastic and i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.22339

    authors: Slaney CY,Möller A,Hertzog PJ,Parker BS

    更新日期:2013-01-01 00:00:00