• Login
    View Item 
    •   JScholarship Home
    • Theses and Dissertations, Electronic (ETDs)
    • ETD -- Doctoral Dissertations
    • View Item
    •   JScholarship Home
    • Theses and Dissertations, Electronic (ETDs)
    • ETD -- Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    COMBINATION IMMUNOTHERAPY TARGETING IMMUNOSUPPRESSIVE SIGNALS IN THE TUMOR MICROENVIRONMENT PREVENTS CANCER PROGRESSION IN BREAST AND PANCREATIC CANCER

    Thumbnail
    View/Open
    KEENAN-DISSERTATION-2015.pdf (4.523Mb)
    Date
    2015-02-17
    Author
    Keenan, Bridget P.
    Metadata
    Show full item record
    Abstract
    Mechanisms of immune tolerance and suppression occur early at the site of developing tumors and inhibit protective responses induced by cancer vaccines, limiting their efficacy in the treatment of cancer. Combinatorial approaches to cancer immunotherapy were used to investigate the simultaneous inhibition of suppressive signals in the tumor microenvironment and induction of protective T cell responses. The inhibition of an immune checkpoint, LAG-3, in a mouse model of HER-2/neu-overexpressing mammary adenocarcinoma was found to improve CD8+ T cell function in an intrinsic manner when used in combination with a GM-CSF-secreting whole cell vaccine and Treg depletion. LAG-3 signaling also altered the phenotype of antigen-presenting cells in the tumor-draining nodes of mice. Early mechanisms of immune tolerance in a mouse model of pancreatic cancer development were characterized and targeted with Treg depletion and an attenuated Listeria vaccine targeting mutated Kras. Local, but not systemic, T cell responses were found to correlate with survival and the alteration of the tumor microenvironment towards an anti-cancer response. In both models of cancer, combination immunotherapy incorporating a vaccine and immunomodulation of the tumor microenvironment was necessary for successful immune responses that inhibited the progression of cancer.
    URI
    http://jhir.library.jhu.edu/handle/1774.2/37977
    Collections
    • ETD -- Doctoral Dissertations

    Related items

    Showing items related by title, author, creator and subject.

    • INVESTIGATION OF BLOOD-BASED BIOMARKERS AND PATTERNS OF DNA METHYLATION IN TUMORS 

      Miller, Brendan Francis (Johns Hopkins UniversityUSA, 2020-03-20)
      One epigenetic hallmark of many cancer types is differential DNA methylation at multiple loci compared to normal tissue. Detection of cancer specific DNA methylation, particularly in the context of a liquid biopsy, could ...
    • Detection of PIK3CA Mutations in Plasma Tumor DNA Circulating in Peripheral Blood of Breast Cancer Patients 

      Valda Toro, Patricia Lourdes (Johns Hopkins University, 2014-04-10)
      Tumor-specific mutations are used as genetic biomarkers for breast cancer diagnosis and prognosis. The detection and quantification of mutations in tumor DNA circulating in peripheral blood offers a non-invasive approach ...
    • INFERRING TUMOR EVOLUTION FROM SOMATIC VARIANT LANDSCAPES 

      Avigdor, Bracha Erlanger; 0000-0002-5031-8303 (Johns Hopkins UniversityUSA, 2017-03-21)
      Breast cancer is the most prevalent type of cancer in the united states with a high mortality rate due to metastases. A rare but aggressive subtype of breast cancer is metaplastic breast cancer. Without complete knowledge ...

    DSpace software copyright © 2002-2016  DuraSpace
    Policies | Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of JScholarshipCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    DSpace software copyright © 2002-2016  DuraSpace
    Policies | Contact Us | Send Feedback
    Theme by 
    Atmire NV