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[{"key": "dc.contributor.advisor", "value": "Kononen, Juha", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Rintanen, Nina", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Lindroos, Emmi", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2018-12-11T07:25:53Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2018-12-11T07:25:53Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2018", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/60553", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Immunologisilla sy\u00f6p\u00e4hoidoilla voidaan saada erinomaisia hoitotuloksia eri kasvaintaudeissa, mutta vain osalla potilaista. Jotta voidaan ennustaa, hy\u00f6tyyk\u00f6 potilas immunologisista hoidoista, on h\u00e4nen kasvaimensa ja immuunij\u00e4rjestelm\u00e4ns\u00e4 ominaispiirteet otettava huomioon. T\u00e4ss\u00e4 tutkimuksessa kartoitettiin useiden kiinte\u00e4n kudoksen kasvainten immunologista tilaa ja etsittiin anti-PD-1 immunoterapiavasteelle prediktiivisi\u00e4 tekij\u00f6it\u00e4. Anti-PD-1 immunoterapialla pyrit\u00e4\u00e4n palauttamaan kasvaimenvastainen immuunivaste est\u00e4m\u00e4ll\u00e4 CD8+T-lymfosyyttien pinnalla olevan\ninhibitorisen PD-1 (programmed death-1) -reseptorin ja siihen sitoutuvan ja useissa kasvaimissa ekspressoituvan PD-1 ligandi 1:n (PD-L1) v\u00e4linen vuorovaikutus. Tutkimuksen aineistona oli 18 Keski-Suomen keskussairaalassa anti-PD-1 immunoterapialla hoidetun potilaan hoitoa edelt\u00e4v\u00e4t kasvainn\u00e4ytteet, joiden CD3+ ja CD8+T-lymfosyyttien lukum\u00e4\u00e4r\u00e4 sek\u00e4 PD-1 ja PD-L1 ekspressio tutkittiin immunohistokemian ja digitaalisen patologian avulla. Kaikissa n\u00e4ytteiss\u00e4 n\u00e4htiin kasvainalueella\nCD3+ ja CD8+T-lymfosyytti-infiltraatio. PD-L1-negatiivisia kasvainn\u00e4ytteit\u00e4 oli seitsem\u00e4n, kuuden PD-L1-positiivisuus oli v\u00e4lill\u00e4 1\u201350 % ja viiden yli 50 %. Kun verrattiin PD-L1-positiivisia PD-L1-negatiivisiin n\u00e4ytteisiin, n\u00e4htiin ett\u00e4 PD-1-positiivisia lymfosyytteja sek\u00e4 kasvaimen reuna-alueen CD8-positiivisia lymfosyytteja oli enemm\u00e4n PD-L1-positiivisissa kuin negatiivisissa n\u00e4ytteiss\u00e4. Kuten aiempien tutkimusten\nperusteella oli oletettavissa, hyv\u00e4 hoitovaste oli yleisempi niill\u00e4 potilailla, joiden n\u00e4ytteet olivat sek\u00e4 lymfosyyttirikkaita ett\u00e4 PD-L1-positiivisia viitaten adaptiiviseen immuuniresistenssiin kasvaimessa. Kasvaimen ja immuunij\u00e4rjestelm\u00e4n v\u00e4linen\nvuorovaikutus on kuitenkin monimutkaista ja t\u00e4ss\u00e4kin tutkimuksessa n\u00e4htiin etteiv\u00e4t kasvaimen lymfosyytti-infiltraation m\u00e4\u00e4r\u00e4, lymfosyyttien PD-1-positiivisuus\ntai kasvainsolujen PD-L1-positiivisuus yksitt\u00e4isin\u00e4 tekij\u00f6in\u00e4 tai yhdistelm\u00e4n\u00e4 kykene riitt\u00e4v\u00e4n hyvin erottamaan huonon ja hyv\u00e4n hoitovasteen saaneiden potilaiden\nkasvainn\u00e4ytteit\u00e4 toisistaan.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Cancer immunotherapy is a promising strategy for cancer treatment, however, it results in durable clinical responses only in a proportion of patients. Thus, there is a growing need to identify biomarkers that could enlighten the interaction between tumor and the immune system and predict treatment outcome. The aim of this study was to describe the immune microenvironment of 18 pre-treatment solid tumor\nspecimens from patients treated with anti-PD-1 immunotherapy in Central Finland Central Hospital. Anti-PD-1 immunotherapy targets the T-lymphocyte inhibitory\nprogrammed cell death-1 (PD-1) receptor activated by programmed cell death-ligand 1 (PD-L1) which is expressed by tumor cells in many cancers. Tumor PD-L1 expression is, thus, considered an important factor predicting the treatment outcome. In addition to determining tumor cell PD-L1 expression, the tumor-infiltrating CD3+ and CD8+T- lymphocytes, as well as their PD-1 expression, were assessed by immunohistochemistry and digital pathology for interrelationships and potential correlations with treatment outcome. A marked infiltration of CD3+ and CD8+T-lymphocytes in the centre of tumor was detected in all specimens. Seven specimens showed PD-L1 expression in less than 1 % of tumor cells, six in 1\u201350 % of tumor cells, and five\nin more than 50 % of tumor cells. There were more PD-1-positive lymphocytes in PD-L1-positive than negative specimens. High PD-L1 expression was associated with higher CD8+T-lymphocyte content in the tumor margin. Five out of six patients who responded well to anti-PD-1 therapy had PD-L1-positive and T-lymphocyte-rich tumor specimen, supporting the hypothesis that the presence of an adaptive immune resistance is associated with better treatment outcome. However, it was seen that the complexity of the tumor-host interplay does make simple immunohistochemical\nbiomarkers challenging in immunotherapy.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2018-12-11T07:25:53Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2018-12-11T07:25:53Z (GMT). No. of bitstreams: 0\n Previous issue date: 2018", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "33", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "biomarkkeri", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "PD-L1", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "PD-1", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "prediktiivinen", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "T-lymfosyytti", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Anti-PD-1 immunoterapiavasteen ennustaminen kiinte\u00e4n kudoksen kasvaimissa", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201812115052", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immuunihoito", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "kasvaimet", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immuunij\u00e4rjestelm\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sy\u00f6p\u00e4hoidot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "markkerit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "hoitovaste", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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