FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2071900609> ?p ?o ?g. }

• W2071900609 abstract "This study aimed to identify potential tolerance signals specific to lower avidity T cells. Cancer vaccines are currently being investigated as a way to activate antigen-specific anti-tumor T cell responses capable of eradicating developing tumors. It is now appreciated that a major barrier to cancer vaccines as therapy are the multiple signals originating from the tumor microenvironment that inhibit the activation of cancer-specific T cells. In addition, the most potent T cells specific for a tumor antigen are often subject to the most potent tolerance mechanisms leaving in place a range of lower avidity T cell sub-populations potentially available for activation. A number of co-regulatory signals play an important role in T cell activation, propagation, function, and/or survival in vivo. However, it is still not clear which mechanisms regulate specific T cell sub-populations within a given T cell repertoire specific for the same cancer antigen. We used the HER-2/ neu ( neu -N) transgenic mouse model of spontaneous mammary tumors in which vaccines targeted against the HER-2/neu protein induce T cell responses against the immunodominant epitope RNEU420-429 with a range of avidities. We created high and low avidity TCR transgenic mice from which isolated T cells can be tracked in the tolerized HER-2/ neu mice in vivo. We first adoptively transferred T cells from the high and low avidity TCR transgenic mice into neu -N mice under different treatment conditions to evaluate the changes in the co-regulatory signaling pathways. Treatment groups included: tumor alone, tumor + a GM-CSF secreting whole cell vaccine, and tumor + vaccine + a T regulatory cell (Treg) depleting agent. The Treg depleting agent cyclophosphamide has been shown to suppress Tregs and allow activation and function of the high avidity T cells but not the low avidity T cells. This suggests that Tregs do not regulate lower avidity T cell populations. The low avidity T cells fail to reject tumor when compared with the high avidity T cells which reject tumor under conditions of vaccine + Treg depletion. We used microarrays to compare signal differences between the high and low avidity T cell populations under each condition, and several genes were identified that were upregulated in the low avidity T cells. Molecules within the survival signaling pathways that specifically demonstrated higher expression were CD24, FasL, and DR5. These molecules were confirmed to have increased protein expression in low avidity T cells when compared with high avidity T cells. Further functional analysis also demonstrated that T cells expressing CD24 and DR5 secrete lower levels of the effector cytokine IFNγ than T cells not expressing those molecules. This increase in proteins involved the cell death pathway correlates with our finding that lower avidity T cells have a shorter survival than higher avidity T cells in the tolerant mice under all treatment conditions. Currently pro-survival therapies are being conducted to determine if survival and function of the low avidity T cells can be altered through modulation of each upregulated pathway. These studies should identify novel combinatorial immune based therapies that engage multiple components of the T cell repertoire and enhance the overall anti-tumor activity of vaccines in vivo.Citation Format: Chelsea M. Black, Todd D. Armstrong, Elizabeth M. Jaffee. Low avidity tumor-specific CD8+ T cells are regulated by increased expression of proapoptotic proteins in tolerant mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B54." @default.
• W2071900609 created "2016-06-24" @default.
• W2071900609 creator A5001768193 @default.
• W2071900609 creator A5050642902 @default.
• W2071900609 creator A5077438023 @default.
• W2071900609 date "2013-01-01" @default.
• W2071900609 modified "2023-09-27" @default.
• W2071900609 title "Abstract B54: Low avidity tumor-specific CD8+ T cells are regulated by increased expression of proapoptotic proteins in tolerant mice." @default.
• W2071900609 doi "https://doi.org/10.1158/1538-7445.tumimm2012-b54" @default.
• W2071900609 hasPublicationYear "2013" @default.
• W2071900609 type Work @default.
• W2071900609 sameAs 2071900609 @default.
• W2071900609 citedByCount "0" @default.
• W2071900609 crossrefType "proceedings-article" @default.
• W2071900609 hasAuthorship W2071900609A5001768193 @default.
• W2071900609 hasAuthorship W2071900609A5050642902 @default.
• W2071900609 hasAuthorship W2071900609A5077438023 @default.
• W2071900609 hasConcept C147483822 @default.
• W2071900609 hasConcept C154317977 @default.
• W2071900609 hasConcept C167672396 @default.
• W2071900609 hasConcept C179223381 @default.
• W2071900609 hasConcept C19317047 @default.
• W2071900609 hasConcept C195616568 @default.
• W2071900609 hasConcept C202751555 @default.
• W2071900609 hasConcept C203014093 @default.
• W2071900609 hasConcept C2776090121 @default.
• W2071900609 hasConcept C2776107976 @default.
• W2071900609 hasConcept C2777701055 @default.
• W2071900609 hasConcept C2777702733 @default.
• W2071900609 hasConcept C2778830056 @default.
• W2071900609 hasConcept C2780674031 @default.
• W2071900609 hasConcept C502942594 @default.
• W2071900609 hasConcept C54355233 @default.
• W2071900609 hasConcept C86803240 @default.
• W2071900609 hasConcept C8840205 @default.
• W2071900609 hasConcept C8891405 @default.
• W2071900609 hasConcept C90375314 @default.
• W2071900609 hasConceptScore W2071900609C147483822 @default.
• W2071900609 hasConceptScore W2071900609C154317977 @default.
• W2071900609 hasConceptScore W2071900609C167672396 @default.
• W2071900609 hasConceptScore W2071900609C179223381 @default.
• W2071900609 hasConceptScore W2071900609C19317047 @default.
• W2071900609 hasConceptScore W2071900609C195616568 @default.
• W2071900609 hasConceptScore W2071900609C202751555 @default.
• W2071900609 hasConceptScore W2071900609C203014093 @default.
• W2071900609 hasConceptScore W2071900609C2776090121 @default.
• W2071900609 hasConceptScore W2071900609C2776107976 @default.
• W2071900609 hasConceptScore W2071900609C2777701055 @default.
• W2071900609 hasConceptScore W2071900609C2777702733 @default.
• W2071900609 hasConceptScore W2071900609C2778830056 @default.
• W2071900609 hasConceptScore W2071900609C2780674031 @default.
• W2071900609 hasConceptScore W2071900609C502942594 @default.
• W2071900609 hasConceptScore W2071900609C54355233 @default.
• W2071900609 hasConceptScore W2071900609C86803240 @default.
• W2071900609 hasConceptScore W2071900609C8840205 @default.
• W2071900609 hasConceptScore W2071900609C8891405 @default.
• W2071900609 hasConceptScore W2071900609C90375314 @default.
• W2071900609 hasLocation W20719006091 @default.
• W2071900609 hasOpenAccess W2071900609 @default.
• W2071900609 hasPrimaryLocation W20719006091 @default.
• W2071900609 hasRelatedWork W1517459791 @default.
• W2071900609 hasRelatedWork W1965237750 @default.
• W2071900609 hasRelatedWork W2024447272 @default.
• W2071900609 hasRelatedWork W2062807307 @default.
• W2071900609 hasRelatedWork W2065648686 @default.
• W2071900609 hasRelatedWork W2084372022 @default.
• W2071900609 hasRelatedWork W2089669180 @default.
• W2071900609 hasRelatedWork W2098772563 @default.
• W2071900609 hasRelatedWork W2149639357 @default.
• W2071900609 hasRelatedWork W2231305303 @default.
• W2071900609 hasRelatedWork W2327919443 @default.
• W2071900609 hasRelatedWork W2331750502 @default.
• W2071900609 hasRelatedWork W2547595918 @default.
• W2071900609 hasRelatedWork W2558914122 @default.
• W2071900609 hasRelatedWork W2565675911 @default.
• W2071900609 hasRelatedWork W2886642793 @default.
• W2071900609 hasRelatedWork W2905362680 @default.
• W2071900609 hasRelatedWork W2906288459 @default.
• W2071900609 hasRelatedWork W2997076162 @default.
• W2071900609 hasRelatedWork W3096232019 @default.
• W2071900609 isParatext "false" @default.
• W2071900609 isRetracted "false" @default.
• W2071900609 magId "2071900609" @default.
• W2071900609 workType "article" @default.