Overcoming immunosuppression to enhance a p53MVA vaccine.

Abstract:

:A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents to deliver clinical benefit. Here, we outline our rationale for combining p53MVA with immunomodulatory chemotherapy in a forthcoming trial.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Hardwick N,Chung V,Cristea M,Ellenhorn JD,Diamond DJ

doi

10.4161/21624011.2014.958949

subject

Has Abstract

pub_date

2014-12-15 00:00:00

pages

e958949

issue

10

eissn

2162-4011

issn

2162-402X

pii

958949

journal_volume

3

pub_type

杂志文章
  • Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression.

    abstract::Antitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. A...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1518672

    authors: Tan Z,Liu L,Chiu MS,Cheung KW,Yan CW,Yu Z,Lee BK,Liu W,Man K,Chen Z

    更新日期:2018-10-16 00:00:00

  • Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy.

    abstract::Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antit...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1188244

    authors: Azuma M,Takeda Y,Nakajima H,Sugiyama H,Ebihara T,Oshiumi H,Matsumoto M,Seya T

    更新日期:2016-05-19 00:00:00

  • Immune cells in pancreatic cancer: Joining the dark side.

    abstract::Pancreatic tumors are rich in immune cell infiltrates that include CD4+ T-cell subsets encompassing both regulatory T cells and TH17 cells. Rather than protecting the organism by exerting an anticancer effect, these T-cell subsets promote tumor formation. Thus, re-activation of antitumor immunity should be investigate...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29125

    authors: Zhang Y,McAllister F,Pasca di Magliano M

    更新日期:2014-06-05 00:00:00

  • Immunomodulation of the tumor microenvironment by Toll-like receptor-3 (TLR3) ligands.

    abstract::In hepatocellular carcinoma (HCC) patients, the intratumoral expression of Toll-like receptor-3 (TLR3) correlates with prolonged survival. We demonstrated that TLR3 ligands can operate through three independent mechanisms: by directly killing TLR3-expressing cancer cells, by inducing T- and natural killer (NK)-cell in...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.23493

    authors: Chew V,Abastado JP

    更新日期:2013-04-01 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

  • Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling.

    abstract::Esophageal cancer-related gene 4 (Ecrg4), a hormone-like peptide, is thought to be a tumor suppressor, however, little is known about the mechanism of how Ecrg4 suppresses tumorigenesis. Here, we show that the ecrg4 null glioma-initiating cell (GIC) line, which was generated from neural stem cells of ecrg4 knockout (K...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1242547

    authors: Moriguchi T,Kaneumi S,Takeda S,Enomoto K,Mishra SK,Miki T,Koshimizu U,Kitamura H,Kondo T

    更新日期:2016-10-14 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

  • Trial watch: dietary interventions for cancer therapy.

    abstract::Dietary interventions have a profound impact on whole body metabolism, including oncometabolism (the metabolic features allowing cancer cells to proliferate) and immunometabolism (the catabolic and anabolic reactions that regulate immune responses). Recent preclinical studies demonstrated that multiple dietary changes...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2019.1591878

    authors: Lévesque S,Pol JG,Ferrere G,Galluzzi L,Zitvogel L,Kroemer G

    更新日期:2019-04-03 00:00:00

  • EBV infection determines the immune hallmarks of plasmablastic lymphoma.

    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

    authors: Gravelle P,Péricart S,Tosolini M,Fabiani B,Coppo P,Amara N,Traverse-Gléhen A,Van Acker N,Brousset P,Fournie JJ,Laurent C

    更新日期:2018-07-30 00:00:00

  • Absence of myeloperoxidase and CD8 positive cells in colorectal cancer infiltrates identifies patients with severe prognosis.

    abstract::Colorectal cancer (CRC) infiltration by cells expressing myeloperoxidase (MPO) or CD8 positive T lymphocytes has been shown to be independently associated with favorable prognosis. We explored the relationship occurring between CD8+ and MPO+ cell CRC infiltration, its impact on clinical-pathological features and its p...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1050574

    authors: Däster S,Eppenberger-Castori S,Hirt C,Soysal SD,Delko T,Nebiker CA,Weixler B,Amicarella F,Iezzi G,Governa V,Padovan E,Mele V,Sconocchia G,Heberer M,Terracciano L,Kettelhack C,Oertli D,Spagnoli GC,von Holzen U,Tornil

    更新日期:2015-05-29 00:00:00

  • Replenish the source within: Rescuing tumor-infiltrating lymphocytes by double checkpoint blockade.

    abstract::We have recently reported that the PD-1 and CTLA4 signaling pathways are active in both effector and regulatory T cells, causing profound immune dysfunctions in the tumor microenvironment. In line with this notion, the dual blockade of PD-1- and CTLA4-conveyed signals may exert robust therapeutic effects. Here, we dis...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.25912

    authors: Duraiswamy J,Freeman G,Coukos G

    更新日期:2013-10-01 00:00:00

  • Ménage à trois: Sustained therapeutic anti-tumor immunity requires multiple partners in malignant glioma.

    abstract::Glioblastoma is an aggressive primary brain cancer. Given our interest in novel immunotherapies, we have recently shown that inhibiting CTLA-4, PD-L1 and IDO results in a dramatic survival advantage in mice with brain tumors. Our preclinical study supports the rapid translation of this approach into phase I clinical t...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28927

    authors: Wainwright DA,Lesniak MS

    更新日期:2014-05-15 00:00:00

  • MDR1 in immunity: friend or foe?

    abstract::MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1499388

    authors: Bossennec M,Di Roio A,Caux C,Ménétrier-Caux C

    更新日期:2018-09-06 00:00:00

  • Sustained CD4+ T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide.

    abstract::Prolonged lymphopenia correlating with decreased survival commonly occurs among glioma patients undergoing radiation therapy (RT) and temozolomide (TMZ) treatment. To better understand the pathophysiology of this phenomenon, we prospectively monitored serum cytokine levels and lymphocyte subsets in 15 high-grade gliom...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.27357

    authors: Ellsworth S,Balmanoukian A,Kos F,Nirschl CJ,Nirschl TR,Grossman SA,Luznik L,Drake CG

    更新日期:2014-01-01 00:00:00

  • Fbxw7 suppresses cancer metastasis by inhibiting niche formation.

    abstract::Fbxw7 has been identified as an oncosuppressor protein in many types of cancer. We have recently shown that loss of Fbxw7 in bone marrow-derived stromal cells (BMSCs) promotes cancer metastasis by increasing production of the chemokine CCL2, which attracts monocytic myeloid-derived suppressor cells (Mo-MDSCs) and macr...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1022308

    authors: Yumimoto K,Nakayama KI

    更新日期:2015-06-03 00:00:00

  • Fusions between dendritic cells and whole tumor cells as anticancer vaccines.

    abstract::Various strategies have been developed to deliver tumor-associated antigens (TAAs) to dendritic cells (DCs). Among these, the fusion of DCs and whole cancer cells can process a broad array of TAAs, including hitherto unidentified molecules, and present them in complex with MHC Class I and II molecules and in the conte...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24437

    authors: Koido S,Homma S,Okamoto M,Namiki Y,Takakura K,Uchiyama K,Kajihara M,Arihiro S,Imazu H,Arakawa H,Kan S,Komita H,Ito M,Ohkusa T,Gong J,Tajiri H

    更新日期:2013-05-01 00:00:00

  • From cell biology to immunology: Controlling metastatic progression of cancer via microRNA regulatory networks.

    abstract::Recently, the study of microRNAs has expanded our knowledge of the fundamental processes of cancer biology and the underlying mechanisms behind tumor metastasis. Extensive research in the fields of microRNA and its novel mechanisms of actions against various cancers has more recently led to the trial of a first cancer...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2016.1230579

    authors: Park JH,Theodoratou E,Calin GA,Shin JI

    更新日期:2016-09-09 00:00:00

  • Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory.

    abstract::The benefits of anti-cancer agents extend beyond direct tumor killing. One aspect of cell death is the potential to release antigens that initiate adaptive immune responses. Here, a diffusion enhanced formulation, INT230-6, containing potent anti-cancer cytotoxic agents, was administered intratumorally into large (app...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1625687

    authors: Bloom AC,Bender LH,Tiwary S,Pasquet L,Clark K,Jiang T,Xia Z,Morales-Kastresana A,Jones JC,Walters I,Terabe M,Berzofsky JA

    更新日期:2019-07-16 00:00:00

  • Oncolytic viruses: how "lytic" must they be for therapeutic efficacy?

    abstract::Oncolytic viruses (OVs) preferentially target and kill cancer cells without affecting healthy cells through a multi-modal mechanism of action. While historically the direct killing activity of OVs was considered the primary mode of action, initiation or augmentation of a host antitumor immune response is now considere...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2019.1596006

    authors: Davola ME,Mossman KL

    更新日期:2019-03-28 00:00:00

  • Bone marrow provides an environment that prevents suppression of therapeutic graft-vs.-tumor immunity by regulatory T cells.

    abstract::Regulatory T cells (Tregs) can prevent graft-vs.-host disease as induced by the infusion of donor lymphocytes to cancer patients, but often they also suppress therapeutic antitumor immunity. We discuss an exception to this phenomenon, exemplifying how the milieu provided by the bone marrow may neutralize Tregs to allo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24659

    authors: Guichelaar T,Mutis T

    更新日期:2013-07-01 00:00:00

  • The extent to which melanoma alters tissue-resident dendritic cell function correlates with tumorigenicity.

    abstract::We have shown that melanoma-derived factors alter the function of differentiated tissue-resident dendritic cells (DC) in a tumorigenicity-dependent manner. Soluble factors, including TGFβ1 and VEGF-A, contributed to dendritic cell dysfunction associated with a highly-aggressive melanoma and conferred a phenotype upon ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1069462

    authors: Hargadon KM

    更新日期:2015-08-12 00:00:00

  • The STING agonist DMXAA triggers a cooperation between T lymphocytes and myeloid cells that leads to tumor regression.

    abstract::Regressing tumors are usually associated with a large immune infiltrate, but the molecular and cellular interactions that govern a successful anti-tumor immunity remain elusive. Here, we have triggered type I Interferon (IFN) signaling in a breast tumor model (MMTV-PyMT) using 5,6-dimethylxanthenone-4-acetic acid (DMX...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1346765

    authors: Weiss JM,Guérin MV,Regnier F,Renault G,Galy-Fauroux I,Vimeux L,Feuillet V,Peranzoni E,Thoreau M,Trautmann A,Bercovici N

    更新日期:2017-07-07 00:00:00

  • Targeted overexpression of prostacyclin synthase inhibits lung tumor progression by recruiting CD4+ T lymphocytes in tumors that express MHC class II.

    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

    authors: Li HY,McSharry M,Walker D,Johnson A,Kwak J,Bullock B,Neuwelt A,Poczobutt JM,Sippel TR,Keith RL,Weiser-Evans MCM,Clambey E,Nemenoff RA

    更新日期:2018-02-13 00:00:00

  • IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors.

    abstract::Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in prim...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1494110

    authors: Gupta S,Jain A,Syed SN,Snodgrass RG,Pflüger-Müller B,Leisegang MS,Weigert A,Brandes RP,Ebersberger I,Brüne B,Namgaladze D

    更新日期:2018-07-30 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

  • Local Salmonella immunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor.

    abstract::The efficacy of antitumoral responses can be increased using combinatorial vaccine strategies. We recently showed that vaccination could be optimized by local administration of diverse molecular or bacterial agents to target and augment antitumoral CD8 T cells in the genital mucosa (GM) and increase regression of cerv...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1016697

    authors: Domingos-Pereira S,Hojeij R,Reggi E,Derré L,Chevalier MF,Romero P,Jichlinski P,Nardelli-Haefliger D

    更新日期:2015-05-22 00:00:00

  • Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer.

    abstract::Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1486953

    authors: Hagihara K,Chan S,Zhang L,Oh DY,Wei XX,Simko J,Fong L

    更新日期:2018-10-01 00:00:00

  • Tumor-infiltrating follicular helper T cells: The new kids on the block.

    abstract::By analyzing CD4+ lymphocytes in human breast carcinomas, we have recently uncovered the presence of follicular helper T cells in lesions exhibiting an extensive immune infiltrate. The presence of these specialized CD4+ T cells, which localize to the germinal centers of peritumoral tertiary lymphoid structures found i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26066

    authors: Gu-Trantien C,Willard-Gallo K

    更新日期:2013-10-01 00:00:00

  • Immunosurveillance in esophageal carcinoma: The decisive impact of regulatory T cells.

    abstract::Neoadjuvant radiochemotherapy of esophageal carcinomas causes a variable degree of depletion of tumor-infiltrating FOXP3+ regulatory T cells (Tregs). The frequency of local Tregs in the operative specimens negatively correlates with the pathological response and overall patient survival. These results underscore the i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1064581

    authors: Vacchelli E,Semeraro M,Adam J,Dartigues P,Zitvogel L,Kroemer G

    更新日期:2015-07-01 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