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Cover for A GENOME-SCALE CRISPR SCREEN TO IDENTIFY ESSENTIAL GENES FOR THE EFFECTOR FUNCTION OF CYTOTOXIC T LYMPHOCYTES
dc.contributor.advisorRestifo, Nicholas Pen
dc.contributor.advisorWeiner, Louisen
dc.creatoren
dc.date.accessioned2017-01-09T18:50:11Zen
dc.date.created2017en
dc.date.issueden
dc.date.submitted01/01/2016en
dc.identifier.otherAPT-BAG: georgetown.edu.10822_1042939.tar;APT-ETAG: 3ab6d6c4b0657bbae44ec7f5dc7b59f5; APT-DATE: 2017-01-30_12:03:54en
dc.identifier.urien
dc.descriptionPh.D.en
dc.description.abstractSomatic gene mutations and dysregulations can alter the vulnerability of a cancer cell to T cell based immune selection. To systematically identify genes that positively regulate the sensitivity of cancer cells to T cell-mediated cytolysis, we developed a two cell-type (2CT) functional screening platform by combining human T cell engineering and CRISPR (Clustered regularly interspaced short palindromic repeats) genome editing. Using the 2CT genome-scale perturbation screen in melanoma cells, we identified and validated multiple genes whose loss impaired the effector function of T cells. Moreover, we uncover a group of genes from these screens that correlates with cytolytic activity across the majority of the cancer types, reflecting context independence of these genes in the modulation of inherent T cell responses in multiple cancers. This study demonstrates the broad applicability of 2CT CRISPR screens to study the interaction of cancer cells with immune cells and identify novel therapeutic targets for cellular therapies.en
dc.formatPDFen
dc.format.extent110 leavesen
dc.languageenen
dc.publisherGeorgetown Universityen
dc.sourceGeorgetown University-Graduate School of Arts & Sciencesen
dc.sourceTumor Biologyen
dc.subjectCancer Immunotherapyen
dc.subjectCRISPR Cas9en
dc.subjectCytotoxic T cellsen
dc.subjectGenome Engineeringen
dc.subjectGenome-wide screensen
dc.subjectImmune Evasionen
dc.subject.lcshImmunologyen
dc.subject.otherImmunologyen
dc.titleA GENOME-SCALE CRISPR SCREEN TO IDENTIFY ESSENTIAL GENES FOR THE EFFECTOR FUNCTION OF CYTOTOXIC T LYMPHOCYTESen
dc.typethesisen
gu.embargo.lift-date2019-01-09en
gu.embargo.termsrestricted-2-yearsen
dc.identifier.orcid0000-0001-8030-7771en


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