B cell-Derived IL35 Drives STAT3-Dependent CD8+ T-cell Exclusion in Pancreatic Cancer.

Abstract:

:Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by a paucity of tumor-proximal CD8+ T cells and resistance to immunotherapeutic interventions. Cancer-associated mechanisms that elicit CD8+ T-cell exclusion and resistance to immunotherapy are not well-known. Here, using a Kras- and p53-driven model of PDA, we describe a mechanism of action for the protumorigenic cytokine IL35 through STAT3 activation in CD8+ T cells. Distinct from its action on CD4+ T cells, IL35 signaling in gp130+CD8+ T cells activated the transcription factor STAT3, which antagonized intratumoral infiltration and effector function of CD8+ T cells via suppression of CXCR3, CCR5, and IFNγ expression. Inhibition of STAT3 signaling in tumor-educated CD8+ T cells improved PDA growth control upon adoptive transfer to tumor-bearing mice. We showed that activation of STAT3 in CD8+ T cells was driven by B cell- but not regulatory T cell-specific production of IL35. We also demonstrated that B cell-specific deletion of IL35 facilitated CD8+ T-cell activation independently of effector or regulatory CD4+ T cells and was sufficient to phenocopy therapeutic anti-IL35 blockade in overcoming resistance to anti-PD-1 immunotherapy. Finally, we identified a circulating IL35+ B-cell subset in patients with PDA and demonstrated that the presence of IL35+ cells predicted increased occurrence of phosphorylated (p)Stat3+CXCR3-CD8+ T cells in tumors and inversely correlated with a cytotoxic T-cell signature in patients. Together, these data identified B cell-mediated IL35/gp130/STAT3 signaling as an important direct link to CD8+ T-cell exclusion and immunotherapy resistance in PDA.

journal_name

Cancer Immunol Res

authors

Mirlekar B,Michaud D,Lee SJ,Kren NP,Harris C,Greene K,Goldman EC,Gupta GP,Fields RC,Hawkins WG,DeNardo DG,Rashid NU,Yeh JJ,McRee AJ,Vincent BG,Vignali DAA,Pylayeva-Gupta Y

doi

10.1158/2326-6066.CIR-19-0349

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

292-308

issue

3

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-19-0349

journal_volume

8

pub_type

杂志文章
  • Dysregulated NF-κB-Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma.

    abstract::Therapeutic cancer vaccines targeting melanoma-associated antigens are commonly immunogenic but are rarely effective in promoting objective clinical responses. To identify critical molecules for activation of effective antitumor immunity, we have profiled autologous dendritic cell (DC) vaccines used to treat 35 patien...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-20-0274

    authors: Maurer DM,Adamik J,Santos PM,Shi J,Shurin MR,Kirkwood JM,Storkus WJ,Butterfield LH

    更新日期:2020-12-01 00:00:00

  • Activated Eosinophils Exert Antitumorigenic Activities in Colorectal Cancer.

    abstract::Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy but only benefit a subset of patients, especially in colorectal cancer. Thus, additional insight into the tumor microenvironment (TME) is required. Eosinophils are bone marrow-derived cells that have been largely studied in the context of aller...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-18-0494

    authors: Reichman H,Itan M,Rozenberg P,Yarmolovski T,Brazowski E,Varol C,Gluck N,Shapira S,Arber N,Qimron U,Karo-Atar D,Lee JJ,Munitz A

    更新日期:2019-03-01 00:00:00

  • Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma.

    abstract::Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审

    doi:10.1158/2326-6066.CIR-13-0082

    authors: Barker CA,Postow MA,Khan SA,Beal K,Parhar PK,Yamada Y,Lee NY,Wolchok JD

    更新日期:2013-08-01 00:00:00

  • Targeting CD20+ Aggressive B-cell Non-Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice.

    abstract::The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-14-0114

    authors: Chu Y,Hochberg J,Yahr A,Ayello J,van de Ven C,Barth M,Czuczman M,Cairo MS

    更新日期:2015-04-01 00:00:00

  • CAR-T Cells Surface-Engineered with Drug-Encapsulated Nanoparticles Can Ameliorate Intratumoral T-cell Hypofunction.

    abstract::One limiting factor of CAR T-cell therapy for treatment of solid cancers is the suppressive tumor microenvironment (TME), which inactivates the function of tumor-infiltrating lymphocytes (TIL) through the production of immunosuppressive molecules, such as adenosine. Adenosine inhibits the function of CD4+ and CD8+ T c...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-17-0502

    authors: Siriwon N,Kim YJ,Siegler E,Chen X,Rohrs JA,Liu Y,Wang P

    更新日期:2018-07-01 00:00:00

  • IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells.

    abstract::Macrophage-mediated cytotoxicity is controlled by surface receptor expression and activation. Despite the numerous studies documenting the role of macrophage C-type lectin receptors (CLR) in pathogen elimination, little is known about their contribution to antitumor responses. Here, we report that IL13 inhibits T-cell...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-18-0213

    authors: Alaeddine M,Prat M,Poinsot V,Gouazé-Andersson V,Authier H,Meunier E,Lefèvre L,Alric C,Dardenne C,Bernad J,Alric L,Segui B,Balard P,Couderc F,Couderc B,Pipy B,Coste A

    更新日期:2019-02-01 00:00:00

  • Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance.

    abstract::Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-16-0400

    authors: Hennequart M,Pilotte L,Cane S,Hoffmann D,Stroobant V,Plaen E,Van den Eynde BJ

    更新日期:2017-08-01 00:00:00

  • The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell Immunosurveillance and Acute Myeloid Leukemia.

    abstract::The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly,...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-17-0212

    authors: Nuebling T,Schumacher CE,Hofmann M,Hagelstein I,Schmiedel BJ,Maurer S,Federmann B,Rothfelder K,Roerden M,Dörfel D,Schneider P,Jung G,Salih HR

    更新日期:2018-02-01 00:00:00

  • Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity.

    abstract::High levels of human telomerase reverse transcriptase (hTERT) are detected in more than 85% of human cancers. Immunologic analysis supports that hTERT is a widely applicable target recognized by T cells and can be potentially studied as a broad cancer immunotherapeutic, or a unique line of defense against tumor recurr...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0001

    authors: Yan J,Pankhong P,Shin TH,Obeng-Adjei N,Morrow MP,Walters JN,Khan AS,Sardesai NY,Weiner DB

    更新日期:2013-09-01 00:00:00

  • Clinical Response of a Patient to Anti-PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors.

    abstract::Anti-Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers, and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCT). Neither the clinical activity of anti-PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-16-0087

    authors: Shah S,Ward JE,Bao R,Hall CR,Brockstein BE,Luke JJ

    更新日期:2016-11-01 00:00:00

  • Insights into Tumor-Associated Tertiary Lymphoid Structures: Novel Targets for Antitumor Immunity and Cancer Immunotherapy.

    abstract::Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审

    doi:10.1158/2326-6066.CIR-20-0432

    authors: Rodriguez AB,Engelhard VH

    更新日期:2020-11-01 00:00:00

  • Report on the Third FDA-AACR Oncology Dose-Finding Workshop.

    abstract::The FDA-AACR Oncology Dose-Finding Workshop, Part 3, was held in Washington, DC, on July 20, 2017, as a continuation of the previous two collaborative dose-finding and optimization workshops presented by the FDA and AACR. This year's workshop focused on combination therapy with immune-oncology agents and best practice...

    journal_title:Cancer immunology research

    pub_type:

    doi:10.1158/2326-6066.CIR-17-0590

    authors: Emens LA,Bruno R,Rubin EH,Jaffee EM,McKee AE

    更新日期:2017-12-01 00:00:00

  • Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments.

    abstract::Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of cancers of hematopoietic origin. In the immunosuppressive solid tumor environment, CAR T cells encounter obstacles that compromise their efficacy. We developed a strategy to address these barriers by having CAR T cells secrete single-domai...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-19-0734

    authors: Xie YJ,Dougan M,Ingram JR,Pishesha N,Fang T,Momin N,Ploegh HL

    更新日期:2020-04-01 00:00:00

  • Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma.

    abstract::CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with ma...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-14-0180

    authors: Saito Y,Ohnishi K,Miyashita A,Nakahara S,Fujiwara Y,Horlad H,Motoshima T,Fukushima S,Jinnin M,Ihn H,Takeya M,Komohara Y

    更新日期:2015-12-01 00:00:00

  • Untreated stage IV melanoma patients exhibit abnormal monocyte phenotypes and decreased functional capacity.

    abstract::Monocytes may contribute to tumor progression in part by mediating tumor-induced immunosuppression. Alterations to the monocyte populations and functions in untreated patients with late-stage melanoma are not fully understood. To characterize these alterations, we compared the frequency, phenotype, and functional capa...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0094

    authors: Chavan R,Salvador D,Gustafson MP,Dietz AB,Nevala W,Markovic SN

    更新日期:2014-03-01 00:00:00

  • Effect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial.

    abstract::Vaccination of patients with ovarian cancer with overlapping long peptides (OLP) from cancer-testis antigen NY-ESO-1 and poly-ICLC in Montanide-ISA-51 (Montanide) was found to consistently induce integrated immune responses (antibody, CD4(+), and CD8(+) T cells). Using detailed methods, we investigated the respective ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0089

    authors: Tsuji T,Sabbatini P,Jungbluth AA,Ritter E,Pan L,Ritter G,Ferran L,Spriggs D,Salazar AM,Gnjatic S

    更新日期:2013-11-01 00:00:00

  • Reducing Toxicity of Immune Therapy Using Aptamer-Targeted Drug Delivery.

    abstract::Modulating the function of immune receptors with antibodies is ushering in a new era in cancer immunotherapy. With the notable exception of PD-1 blockade used as monotherapy, immune modulation can be associated with significant toxicities that are expected to escalate with the development of increasingly potent immune...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审

    doi:10.1158/2326-6066.CIR-15-0194

    authors: Gilboa E,Berezhnoy A,Schrand B

    更新日期:2015-11-01 00:00:00

  • An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer.

    abstract::A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in non-targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4 monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human monoclon...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0115

    authors: Golden EB,Demaria S,Schiff PB,Chachoua A,Formenti SC

    更新日期:2013-12-01 00:00:00

  • Deciphering the Immunomodulatory Capacity of Oncolytic Vaccinia Virus to Enhance the Immune Response to Breast Cancer.

    abstract::Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-19-0703

    authors: Umer BA,Noyce RS,Franczak BC,Shenouda MM,Kelly RG,Favis NA,Desaulniers M,Baldwin TA,Hitt MM,Evans DH

    更新日期:2020-05-01 00:00:00

  • IL1α Antagonizes IL1β and Promotes Adaptive Immune Rejection of Malignant Tumors.

    abstract::We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-19-0552

    authors: Tian T,Lofftus S,Pan Y,Stingley CA,King SL,Zhao J,Pan TY,Lock R,Marglous JW,Liu K,Widlund HR,Fuhlbrigge RC,Cichowski K,Kupper TS

    更新日期:2020-05-01 00:00:00

  • Possible Interaction of Anti-PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases.

    abstract::Delayed radiation-induced vasculitic leukoencephalopathy related to stereotactic radiosurgery (SRS) of brain metastases has been reported to manifest clinically 9 to 18 months after treatment. Immune-modulating therapies have been introduced to treatment regimens for malignancies with metastatic predilection to the br...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-15-0238

    authors: Alomari AK,Cohen J,Vortmeyer AO,Chiang A,Gettinger S,Goldberg S,Kluger HM,Chiang VL

    更新日期:2016-06-01 00:00:00

  • Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade.

    abstract::Immune checkpoint inhibitors promote T cell-mediated killing of cancer cells; however, only a subset of patients benefit from the treatment. A possible reason for this limitation may be that the tumor microenvironment (TME) is immune privileged, which may exclude cytotoxic T cells from the vicinity of cancer cells. Th...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-16-0303

    authors: Zboralski D,Hoehlig K,Eulberg D,Frömming A,Vater A

    更新日期:2017-11-01 00:00:00

  • CALGB 150905 (Alliance): rituximab broadens the antilymphoma response by activating unlicensed NK cells.

    abstract::Natural killer (NK) cells contribute to clinical responses in patients treated with rituximab, but the rules determining NK-cell responsiveness to mAb therapies are poorly defined. A deeper understanding of the mechanisms responsible for antibody-dependent cellular cytotoxicity (ADCC) could yield useful biomarkers for...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0158

    authors: Du J,Lopez-Verges S,Pitcher BN,Johnson J,Jung SH,Zhou L,Hsu K,Czuczman MS,Cheson B,Kaplan L,Lanier LL,Venstrom JM

    更新日期:2014-09-01 00:00:00

  • Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer.

    abstract::Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-pa...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-16-0125

    authors: Cullis J,Siolas D,Avanzi A,Barui S,Maitra A,Bar-Sagi D

    更新日期:2017-03-01 00:00:00

  • Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

    abstract::The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related a...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-17-0220

    authors: Martini DJ,Hamieh L,McKay RR,Harshman LC,Brandao R,Norton CK,Steinharter JA,Krajewski KM,Gao X,Schutz FA,McGregor B,Bossé D,Lalani AA,De Velasco G,Michaelson MD,McDermott DF,Choueiri TK

    更新日期:2018-04-01 00:00:00

  • NetH2pan: A Computational Tool to Guide MHC Peptide Prediction on Murine Tumors.

    abstract::With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB geneti...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-17-0298

    authors: DeVette CI,Andreatta M,Bardet W,Cate SJ,Jurtz VI,Jackson KW,Welm AL,Nielsen M,Hildebrand WH

    更新日期:2018-06-01 00:00:00

  • Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal Cancer.

    abstract::Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating the...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-19-0775

    authors: Ikeda A,Ogino T,Kayama H,Okuzaki D,Nishimura J,Fujino S,Miyoshi N,Takahashi H,Uemura M,Matsuda C,Yamamoto H,Takeda K,Mizushima T,Mori M,Doki Y

    更新日期:2020-06-01 00:00:00

  • Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor.

    abstract::Despite the rapid progress in the development of novel adoptive T-cell therapies, the clinical benefits in treatment of established tumors have remained modest. Several immune evasion mechanisms hinder T-cell entry into tumors and their activity within the tumor. Of note, oncolytic adenoviruses are intrinsically immun...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-14-0220-T

    authors: Tähtinen S,Grönberg-Vähä-Koskela S,Lumen D,Merisalo-Soikkeli M,Siurala M,Airaksinen AJ,Vähä-Koskela M,Hemminki A

    更新日期:2015-08-01 00:00:00

  • Anti-PD-1-Induced Pneumonitis Is Associated with Persistent Imaging Abnormalities in Melanoma Patients.

    abstract::Pneumonitis may complicate anti-programmed death-1 (PD-1) therapy, although symptoms usually resolve with steroids. The long-term effects on respiratory function, however, are not well defined. We screened melanoma patients treated with anti-PD-1, with and without ipilimumab (anti-CTLA-4), and identified 31 patients w...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,多中心研究

    doi:10.1158/2326-6066.CIR-18-0717

    authors: Johnson DB,Taylor KB,Cohen JV,Ayoubi N,Haugh AM,Wang DY,Schlick BD,Voorhees AL,Gage KL,Fintelmann FJ,Sullivan RJ,Eroglu Z,Abramson RG

    更新日期:2019-11-01 00:00:00

  • Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    abstract::Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45...

    journal_title:Cancer immunology research

    pub_type: 杂志文章

    doi:10.1158/2326-6066.CIR-13-0124

    authors: Chen YT,Panarelli NC,Piotti KC,Yantiss RK

    更新日期:2014-05-01 00:00:00