Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1.

Abstract:

:Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation between the expression of PD-L1 and c-Myc. Moreover, the expression of both PD-L1 and c-Myc was associated with poor overall survival. In addition, we confirmed this finding with the PDAC patients in the TCGA database. Using several PDAC cell lines we demonstrated a significant correlation between the expression of PD-L1 and c-Myc. We also found that expression of PD-L1 correlated with high-grade histology. JQ1, an inhibitor of c-Myc inhibited PD-L1 expression and tumor growth. Using xenograft models, we demonstrated that the combination of JQ1 and anti-PD-L1 antibody exerted synergistic inhibition of PDAC growth. Our data demonstrated that the expression of PD-L1 and c-Myc may be helpful prognostic biomarkers, and their inhibition may potentially serve as an effective treatment for PDAC.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Pan Y,Fei Q,Xiong P,Yang J,Zhang Z,Lin X,Pan M,Lu F,Huang H

doi

10.1080/2162402X.2019.1581529

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

e1581529

issue

5

eissn

2162-4011

issn

2162-402X

pii

1581529

journal_volume

8

pub_type

杂志文章
  • Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells.

    abstract::Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1268309

    authors: Cui B,Lu S,Lai L,Xie Y,He J,Xue Y,Xiao P,Pan T,Chen L,Liu Y,Cao X,Wang Q

    更新日期:2017-01-20 00:00:00

  • Flipping the script on macrophages in leiomyosarcoma.

    abstract::Macrophages promote the growth of leiomyosarcoma (LMS), a malignant soft-tissue tumor. CD47 on tumor cells binds to the macrophagic receptor signal regulatory protein α (SIRPα) and prevents phagocytosis. We showed that anti-CD47 monoclonal antibodies (mAbs) allow macrophages to engulf LMS cells and prevent tumor growt...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.20799

    authors: Edris B,Weiskopf K,Weissman IL,van de Rijn M

    更新日期:2012-10-01 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

  • The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers.

    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

    authors: Bertucci F,Finetti P,Birnbaum D,Mamessier E

    更新日期:2015-08-31 00:00:00

  • Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model.

    abstract::LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1338236

    authors: Nestvold J,Wang MY,Camilio KA,Zinöcker S,Tjelle TE,Lindberg A,Haug BE,Kvalheim G,Sveinbjørnsson B,Rekdal Ø

    更新日期:2017-06-16 00:00:00

  • Bendamustine with total body irradiation conditioning yields tolerant T-cells while preserving T-cell-dependent graft-versus-leukemia.

    abstract::Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (B...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1758011

    authors: Stokes J,Hoffman EA,Molina MS,Kummet N,Simpson RJ,Zeng Y,Katsanis E

    更新日期:2020-04-30 00:00:00

  • B cells in esophago-gastric adenocarcinoma are highly differentiated, organize in tertiary lymphoid structures and produce tumor-specific antibodies.

    abstract::Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune respo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1512458

    authors: Schlößer HA,Thelen M,Lechner A,Wennhold K,Garcia-Marquez MA,Rothschild SI,Staib E,Zander T,Beutner D,Gathof B,Gilles R,Cukuroglu E,Göke J,Shimabukuro-Vornhagen A,Drebber U,Quaas A,Bruns CJ,Hölscher AH,Von Bergwelt-Bai

    更新日期:2018-11-02 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

  • Development and validation of an immune-related gene pairs signature in colorectal cancer.

    abstract::Although the outcome of colorectal cancer (CRC) patients has improved significantly with the recent implementation of annual screening programs, reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and CRC progn...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1596715

    authors: Wu J,Zhao Y,Zhang J,Wu Q,Wang W

    更新日期:2019-04-15 00:00:00

  • Rehmannia glutinosa polysaccharide induces toll-like receptor 4 dependent spleen dendritic cell maturation and anti-cancer immunity.

    abstract::Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 m...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1325981

    authors: Xu L,Kwak M,Zhang W,Zeng L,Lee PC,Jin JO

    更新日期:2017-05-12 00:00:00

  • Chronic activation of DNA damage signals causes tumor immune evasion in the chemoresistant niche.

    abstract::DNA damage responses have been proposed as a gatekeeper to block tumorigenesis. We identify unexpected mechanisms whereby ATM-mediated pathway interacts with NFκB inflammatory cascades, leading to upregulation of integrin-αbβ3 on chemoresistant tumor cells. The integrin-αbβ3 is responsible for impeding tumor-specific ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19123

    authors: Jinushi M

    更新日期:2012-05-01 00:00:00

  • Correction.

    abstract::[This corrects the article DOI: 10.1080/2162402X.2015.1031440.]. ...

    journal_title:Oncoimmunology

    pub_type: 已发布勘误

    doi:10.1080/2162402X.2019.1703612

    authors:

    更新日期:2019-12-14 00:00:00

  • Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1+ triple negative breast cancer cells.

    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

    authors: Mohan N,Hosain S,Zhao J,Shen Y,Luo X,Jiang J,Endo Y,Wu WJ

    更新日期:2019-06-06 00:00:00

  • Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma.

    abstract::We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1136044

    authors: Cooper ZA,Reuben A,Spencer CN,Prieto PA,Austin-Breneman JL,Jiang H,Haymaker C,Gopalakrishnan V,Tetzlaff MT,Frederick DT,Sullivan RJ,Amaria RN,Patel SP,Hwu P,Woodman SE,Glitza IC,Diab A,Vence LM,Rodriguez-Canales J,P

    更新日期:2016-02-02 00:00:00

  • Melanoma response to anti-PD-L1 immunotherapy requires JAK1 signaling, but not JAK2.

    abstract::Immunotherapies targeting programmed cell death protein 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), dramatically improve the survival of melanoma patients. However, only ∼40% of treated patients demonstrate a clinical response to single-agent anti-PD-1 therapy. An intact tumor response to type-II i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1438106

    authors: Luo N,Formisano L,Gonzalez-Ericsson PI,Sanchez V,Dean PT,Opalenik SR,Sanders ME,Cook RS,Arteaga CL,Johnson DB,Balko JM

    更新日期:2018-03-06 00:00:00

  • A novel regulation of PD-1 ligands on mesenchymal stromal cells through MMP-mediated proteolytic cleavage.

    abstract::Whether fibroblasts regulate immune response is a crucial issue in the modulation of inflammatory responses. Herein, we demonstrate that foreskin fibroblasts (FFs) potently inhibit CD3+ T cell proliferation through a mechanism involving early apoptosis of activated T cells. Using blocking antibodies, we demonstrate th...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1091146

    authors: Dezutter-Dambuyant C,Durand I,Alberti L,Bendriss-Vermare N,Valladeau-Guilemond J,Duc A,Magron A,Morel AP,Sisirak V,Rodriguez C,Cox D,Olive D,Caux C

    更新日期:2015-10-29 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

  • Host immune response index in gastric cancer identified by comprehensive analyses of tumor immunity.

    abstract::Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1356150

    authors: Park C,Cho J,Lee J,Kang SY,An JY,Choi MG,Lee JH,Sohn TS,Bae JM,Kim S,Kim ST,Park SH,Park JO,Kang WK,Sohn I,Jung SH,Kang MS,Kim KM

    更新日期:2017-08-10 00:00:00

  • Antibody response to cancer/testis (CT) antigens: A prognostic marker in cancer patients.

    abstract::Immune responses to tumor antigens have been reported in cancer patients. However, the relevance of such spontaneous immune responses to the clinical course has not been studied extensively. We showed that the overall survival of patients with antibodies against NY-ESO-1 or XAGE1 (GAGED2a) antigen was prolonged in gas...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.970032

    authors: Ohue Y,Wada H,Oka M,Nakayama E

    更新日期:2014-12-21 00:00:00

  • The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma.

    abstract::Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a subject of intense research, less is known about their biological function espe...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1456612

    authors: Kachler K,Holzinger C,Trufa DI,Sirbu H,Finotto S

    更新日期:2018-04-25 00:00:00

  • Radiotherapy supports protective tumor-specific immunity.

    abstract::Radiotherapy is an important therapeutic option for the treatment of cancer. Growing evidence indicates that, besides inducing an irreversible DNA damage, radiotherapy promotes tumor-specific immune response, which significantly contribute to therapeutic efficacy. We postulate that radiotherapy activates tumor-associa...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21478

    authors: Gupta A,Sharma A,von Boehmer L,Surace L,Knuth A,van den Broek M

    更新日期:2012-12-01 00:00:00

  • Induction of immunogenic cell death by targeting RIG-I-like helicases in pancreatic cancer.

    abstract::RIG-I-like helicases (RLH) are cytosolic sensors for viral RNA inducing type I interferon production. We found that pancreatic cancer cells express functional RLH and are susceptible to RLH-induced apoptosis via intrinsic and extrinsic pathways. Tumor cells displayed features of immunogenic cell death resulting in den...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.955687

    authors: Schnurr M,Duewell P

    更新日期:2014-12-13 00:00:00

  • 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

  • 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

  • PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates.

    abstract::Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival (OS) and a dramatic improvement in patient quality of life. Despite the success of this approach, the number of benefitting patients is limited and there is a need for predictive biomar...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1786888

    authors: Pico de Coaña Y,Wolodarski M,van der Haar Àvila I,Nakajima T,Rentouli S,Lundqvist A,Masucci G,Hansson J,Kiessling R

    更新日期:2020-08-28 00:00:00

  • mRNA-transfected dendritic cell vaccine in combination with metronomic cyclophosphamide as treatment for patients with advanced malignant melanoma.

    abstract:INTRODUCTION:Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen o...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1207842

    authors: Borch TH,Engell-Noerregaard L,Zeeberg Iversen T,Ellebaek E,Met Ö,Hansen M,Andersen MH,Thor Straten P,Svane IM

    更新日期:2016-07-08 00:00:00

  • Colorectal cancer: the first neoplasia found to be under immunosurveillance and the last one to respond to immunotherapy?

    abstract::The first study demonstrating that human colorectal carcinoma (CRC) is under robust immunosurveillance was published a decade ago. Today, it is clear that CRC patients with Stage III lesions abundantly infiltrated by effector memory T cells have a better prognosis than subjects with Stage I neoplasms exhibiting no or ...

    journal_title:Oncoimmunology

    pub_type: 社论

    doi:10.1080/2162402X.2015.1058597

    authors: Kroemer G,Galluzzi L,Zitvogel L,Fridman WH

    更新日期:2015-06-05 00:00:00

  • Alerting the immune system via stromal cells is central to the prevention of tumor growth.

    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

    authors: Issazadeh-Navikas S

    更新日期:2013-12-01 00:00:00

  • Multifunctional γδ T cells and their receptors for targeted anticancer immunotherapy.

    abstract::Human γδ T cells possess broad antitumor reactivity and are involved in the control of viral infections. We have recently described multifunctional γδ T cells induced by cytomegalovirus after allogenic stem cell transplantation, placing γδ T cells and their receptors in the spotlight for the development of novel antic...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.23974

    authors: Scheper W,Gründer C,Kuball J

    更新日期:2013-05-01 00:00:00

  • NKT cell adjuvants in therapeutic vaccines against hematological cancers.

    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

    authors: Mattarollo SR,Smyth MJ

    更新日期:2013-01-01 00:00:00