This study investigated relationships between individual learner differences and the learning of two English structures that differed in their grammatical difficulty. Using a quasi-experimental design, 66 secondary-level learners of English as a foreign language from three intact classes were provided with four hours of instruction on two L2 structures –one considered relatively easy to learn (i.e., past progressive) and the other relatively difficult to learn (i.e. passive construction). The participants were pretested on their knowledge of both structures and posttested immediately after the instruction. Learners’ progress was measured via written grammaticality judgment tests (GJT) and oral production tasks (OPT). The instruments to measure individual learner differences included a computerized language aptitude test, an L1 metalinguistic awareness test, a motivation questionnaire, a backward digit span test, and a learner retrospection questionnaire. The results revealed that aptitude and motivation were the two variables that significantly contributed to learners’ gains with respect to the ‘passive’ and that L1 metalinguistic awareness explained significant variation in learners’ gains regarding the ‘past progressive’. These relationships were observed with learners’ performance on the written but not oral measures. A detailed analysis of the aptitude test components revealed that the grammatical inferencing subtask was significantly related to L2 gains on the ‘passive’ – again only with respect to learners’ performance on the written GJT. The results also revealed that learners with different aptitude profiles (i.e., low, medium, high) benefited differently from instruction on the two target features. High aptitude learners performed better than low aptitude learners on the ‘passive’ as measured by the GJT posttest. With respect to the ‘past progressive’ only learners in the medium aptitude profile group improved significantly on the written GJT. These findings confirm that language aptitude holds a role in language learning but that there are other factors (i.e., motivation and L1 metalinguistic awareness) that also contribute to L2 progress. These results also provide evidence from a classroom-based study that the grammatical difficulty of what is to be learned is a factor in determining what cognitive abilities L2 learners rely on in their efforts to learn a new language.

This study investigated relationships between individual learner differences and the learning of two English structures that differed in their grammatical difficulty. Using a quasi-experimental design, 66 secondary-level learners of English as a foreign language from three intact classes were provided with four hours of instruction on two L2 structures –one considered relatively easy to learn (i.e., past progressive) and the other relatively difficult to learn (i.e. passive construction). The participants were pretested on their knowledge of both structures and posttested immediately after the instruction. Learners’ progress was measured via written grammaticality judgment tests (GJT) and oral production tasks (OPT). The instruments to measure individual learner differences included a computerized language aptitude test, an L1 metalinguistic awareness test, a motivation questionnaire, a backward digit span test, and a learner retrospection questionnaire. The results revealed that aptitude and motivation were the two variables that significantly contributed to learners’ gains with respect to the ‘passive’ and that L1 metalinguistic awareness explained significant variation in learners’ gains regarding the ‘past progressive’. These relationships were observed with learners’ performance on the written but not oral measures. A detailed analysis of the aptitude test components revealed that the grammatical inferencing subtask was significantly related to L2 gains on the ‘passive’ – again only with respect to learners’ performance on the written GJT. The results also revealed that learners with different aptitude profiles (i.e., low, medium, high) benefited differently from instruction on the two target features. High aptitude learners performed better than low aptitude learners on the ‘passive’ as measured by the GJT posttest. With respect to the ‘past progressive’ only learners in the medium aptitude profile group improved significantly on the written GJT. These findings confirm that language aptitude holds a role in language learning but that there are other factors (i.e., motivation and L1 metalinguistic awareness) that also contribute to L2 progress. These results also provide evidence from a classroom-based study that the grammatical difficulty of what is to be learned is a factor in determining what cognitive abilities L2 learners rely on in their efforts to learn a new language.

Esta tese representa o resultado de um estudo teórico que tem por objetivo investigar a constituição dos sentidos da interdisciplinaridade (ID) presentes nas obras de Paulo Freire e Michel Serres, num diálogo aproximativo entre ambos. Para essa finalidade, a pesquisa valeu-se também da contribuição de autores, estudiosos e pesquisadores que versam acerca da ID no âmbito da Educação, ampliando, assim, o diálogo entre Freire e Serres a outras vozes, sem perder a especificidade do tema tratado. Ainda que a ID, genericamente, constitua-se em um conceito polivalente quanto ao campo de sua emergência de sentido e às aplicações práticas de suas apostas, a pesquisa acerca dos sentidos que ela comporta, tanto em Freire como em Serres, nos remete à idéia de que a sua concepção, enquanto diálogo entre as disciplinas, pode e deve ser fecunda em sentidos e significados em relação ao mundo atual e para a formação do novo humano: um ser humano a um tempo científico, responsável e sensível à qualidade da vida como um todo e à própria sobrevida do planeta Terra. Nesta tese conclui-se que há sentidos comuns na hermenêutica da ID presente nas obras de Freire e Serres. São sentidos nucleares que se anunciam a partir do humanismo expresso em seus textos; no projeto de formação do novo humano que transita entre o conhecimento científico e as humanidades, num diálogo interdisciplinar que tem por meta a emergência do tiers-instruit (Serres) e do ser mais (Freire). Esse recurso interdisciplinar, como o próprio conceito recomenda, não anula as disciplinas, mas pede que as mesmas dialoguem entre si numa perspectiva eticamente fértil e conseqüente para a compreensão da unidade na diversidade dos eventos da vida. Trata-se, outrossim, de uma unidade fundada no entendimento da dinâmica dos eventos da vida que são, ao mesmo tempo, constituintes da matéria do real e da consciência que deste podemos possuir. Daí que com Freire e Serres a ID adquire uma propositura de emergência em nível da formação humana. Formar sujeitos responsáveis e conscientes de sua inserção na vida como um todo nos remete à idéia de que a educação pressupõe a sua inscrição na formação científica e técnica com rigores insuspeitos, mas também e ao mesmo tempo à formação humanista, sensível, literária, criadora de espíritos críticos e despertos aos cuidados da vida. Assim, os resultados do estudo desta tese apontam para a retomada da ID como providência pedagógica inadiável em nível da formação do educando em todos os níveis de ensino. Por sua vez, a abordagem hermenêutica, enquanto método de aproximação ao objeto de estudo, reinstala a compreensão da formação ID do ser humano como pronúncia da historicidade e dos pré-juízos (ou juízos prévios) presentes no modo de ser finito da experiência humana, onde o conhecimento traduz o seu presente epocal levando em consideração o legado histórico e cultural das formas com que a linguagem recepciona a compreensão dos textos estudados. / This thesis represents the result of a theoretical study that aims to look into the constitution of the meanings of interdisciplinarity (ID) as revealed by Paulo Freire's and Michel Serres’s works. It also relies upon the contribution of authors, scholars and researchers that deal with ID in the sphere of Education, extending thus the dialogue between Freire and Serres to other voices, without losing the specificity of the theme in focus. Even though, in general terms, ID is a multivocal concept concerning the field of its emergence of meaning and the practical applications of its proposals, the research on the meanings it holds, both in Freire and Serres, refers us to the idea that its conception, while dialogue among disciplines, can and must be fertile in meanings and significations in relation to today’s world and for the formation of the new human: a human being at the same time scientific, responsible and sensitive to the quality of life as a whole and to the survival of the planet Earth. The conclusion herein reached is that there are common meanings in the hermeneutics of ID in the works of Freire and Serres. These are nuclear meanings that announce themselves emerging from the humanism expressed in their texts; in the formation project of the new human that moves between the scientific knowledge and the humanities, in an interdisciplinary dialogue that has for goal the emergence of the tiers-instruit (third instructed)(Serres) and of the ser mais (being plus) (Freire). This interdisciplinary resource, as recommended by the concept itself, does not nullify the disciplines, but requires them to dialogue amongst themselves in an ethically fertile perspective and consequent for the comprehension of unity in the diversity of life’s events. Besides, what is involved is a unity grounded on the understanding of the dynamics of life’s events that are, at the same time, constituents of the matter of the real and of the consciousness that we can have of it. From thence, with Freire and Serres ID acquires a proposition of emergence on the level of the human formation. To form responsible subjects, conscious of their insertion in life as a whole, refers us to the idea that education presupposes its inscription in the scientific and technical formation with definite rigors, but also and at the same time to the humanistic, sensitive, and literary formation, generative of critical minds, awakened to the cares of life. So, the results of the study of this thesis point to the recapture of ID as undelayable pedagogic measure in terms of the student's formation in all learning levels. As for the hermeneutic approach, taken as a method of approaching the object of study, it reinstalls the comprehension of the ID formation of the human being as pronunciation of the historicity and of the pre-judgements (or previous judgements/pre-concepts) embedded in the way of being finite of the human experience, where knowledge reflects its epocal present taking into account the historical and cultural legacy of the forms with which language welcomes the understanding of the studied texts.

Esta tese representa o resultado de um estudo teórico que tem por objetivo investigar a constituição dos sentidos da interdisciplinaridade (ID) presentes nas obras de Paulo Freire e Michel Serres, num diálogo aproximativo entre ambos. Para essa finalidade, a pesquisa valeu-se também da contribuição de autores, estudiosos e pesquisadores que versam acerca da ID no âmbito da Educação, ampliando, assim, o diálogo entre Freire e Serres a outras vozes, sem perder a especificidade do tema tratado. Ainda que a ID, genericamente, constitua-se em um conceito polivalente quanto ao campo de sua emergência de sentido e às aplicações práticas de suas apostas, a pesquisa acerca dos sentidos que ela comporta, tanto em Freire como em Serres, nos remete à idéia de que a sua concepção, enquanto diálogo entre as disciplinas, pode e deve ser fecunda em sentidos e significados em relação ao mundo atual e para a formação do novo humano: um ser humano a um tempo científico, responsável e sensível à qualidade da vida como um todo e à própria sobrevida do planeta Terra. Nesta tese conclui-se que há sentidos comuns na hermenêutica da ID presente nas obras de Freire e Serres. São sentidos nucleares que se anunciam a partir do humanismo expresso em seus textos; no projeto de formação do novo humano que transita entre o conhecimento científico e as humanidades, num diálogo interdisciplinar que tem por meta a emergência do tiers-instruit (Serres) e do ser mais (Freire). Esse recurso interdisciplinar, como o próprio conceito recomenda, não anula as disciplinas, mas pede que as mesmas dialoguem entre si numa perspectiva eticamente fértil e conseqüente para a compreensão da unidade na diversidade dos eventos da vida. Trata-se, outrossim, de uma unidade fundada no entendimento da dinâmica dos eventos da vida que são, ao mesmo tempo, constituintes da matéria do real e da consciência que deste podemos possuir. Daí que com Freire e Serres a ID adquire uma propositura de emergência em nível da formação humana. Formar sujeitos responsáveis e conscientes de sua inserção na vida como um todo nos remete à idéia de que a educação pressupõe a sua inscrição na formação científica e técnica com rigores insuspeitos, mas também e ao mesmo tempo à formação humanista, sensível, literária, criadora de espíritos críticos e despertos aos cuidados da vida. Assim, os resultados do estudo desta tese apontam para a retomada da ID como providência pedagógica inadiável em nível da formação do educando em todos os níveis de ensino. Por sua vez, a abordagem hermenêutica, enquanto método de aproximação ao objeto de estudo, reinstala a compreensão da formação ID do ser humano como pronúncia da historicidade e dos pré-juízos (ou juízos prévios) presentes no modo de ser finito da experiência humana, onde o conhecimento traduz o seu presente epocal levando em consideração o legado histórico e cultural das formas com que a linguagem recepciona a compreensão dos textos estudados. / This thesis represents the result of a theoretical study that aims to look into the constitution of the meanings of interdisciplinarity (ID) as revealed by Paulo Freire's and Michel Serres’s works. It also relies upon the contribution of authors, scholars and researchers that deal with ID in the sphere of Education, extending thus the dialogue between Freire and Serres to other voices, without losing the specificity of the theme in focus. Even though, in general terms, ID is a multivocal concept concerning the field of its emergence of meaning and the practical applications of its proposals, the research on the meanings it holds, both in Freire and Serres, refers us to the idea that its conception, while dialogue among disciplines, can and must be fertile in meanings and significations in relation to today’s world and for the formation of the new human: a human being at the same time scientific, responsible and sensitive to the quality of life as a whole and to the survival of the planet Earth. The conclusion herein reached is that there are common meanings in the hermeneutics of ID in the works of Freire and Serres. These are nuclear meanings that announce themselves emerging from the humanism expressed in their texts; in the formation project of the new human that moves between the scientific knowledge and the humanities, in an interdisciplinary dialogue that has for goal the emergence of the tiers-instruit (third instructed)(Serres) and of the ser mais (being plus) (Freire). This interdisciplinary resource, as recommended by the concept itself, does not nullify the disciplines, but requires them to dialogue amongst themselves in an ethically fertile perspective and consequent for the comprehension of unity in the diversity of life’s events. Besides, what is involved is a unity grounded on the understanding of the dynamics of life’s events that are, at the same time, constituents of the matter of the real and of the consciousness that we can have of it. From thence, with Freire and Serres ID acquires a proposition of emergence on the level of the human formation. To form responsible subjects, conscious of their insertion in life as a whole, refers us to the idea that education presupposes its inscription in the scientific and technical formation with definite rigors, but also and at the same time to the humanistic, sensitive, and literary formation, generative of critical minds, awakened to the cares of life. So, the results of the study of this thesis point to the recapture of ID as undelayable pedagogic measure in terms of the student's formation in all learning levels. As for the hermeneutic approach, taken as a method of approaching the object of study, it reinstalls the comprehension of the ID formation of the human being as pronunciation of the historicity and of the pre-judgements (or previous judgements/pre-concepts) embedded in the way of being finite of the human experience, where knowledge reflects its epocal present taking into account the historical and cultural legacy of the forms with which language welcomes the understanding of the studied texts.

Esta tese representa o resultado de um estudo teórico que tem por objetivo investigar a constituição dos sentidos da interdisciplinaridade (ID) presentes nas obras de Paulo Freire e Michel Serres, num diálogo aproximativo entre ambos. Para essa finalidade, a pesquisa valeu-se também da contribuição de autores, estudiosos e pesquisadores que versam acerca da ID no âmbito da Educação, ampliando, assim, o diálogo entre Freire e Serres a outras vozes, sem perder a especificidade do tema tratado. Ainda que a ID, genericamente, constitua-se em um conceito polivalente quanto ao campo de sua emergência de sentido e às aplicações práticas de suas apostas, a pesquisa acerca dos sentidos que ela comporta, tanto em Freire como em Serres, nos remete à idéia de que a sua concepção, enquanto diálogo entre as disciplinas, pode e deve ser fecunda em sentidos e significados em relação ao mundo atual e para a formação do novo humano: um ser humano a um tempo científico, responsável e sensível à qualidade da vida como um todo e à própria sobrevida do planeta Terra. Nesta tese conclui-se que há sentidos comuns na hermenêutica da ID presente nas obras de Freire e Serres. São sentidos nucleares que se anunciam a partir do humanismo expresso em seus textos; no projeto de formação do novo humano que transita entre o conhecimento científico e as humanidades, num diálogo interdisciplinar que tem por meta a emergência do tiers-instruit (Serres) e do ser mais (Freire). Esse recurso interdisciplinar, como o próprio conceito recomenda, não anula as disciplinas, mas pede que as mesmas dialoguem entre si numa perspectiva eticamente fértil e conseqüente para a compreensão da unidade na diversidade dos eventos da vida. Trata-se, outrossim, de uma unidade fundada no entendimento da dinâmica dos eventos da vida que são, ao mesmo tempo, constituintes da matéria do real e da consciência que deste podemos possuir. Daí que com Freire e Serres a ID adquire uma propositura de emergência em nível da formação humana. Formar sujeitos responsáveis e conscientes de sua inserção na vida como um todo nos remete à idéia de que a educação pressupõe a sua inscrição na formação científica e técnica com rigores insuspeitos, mas também e ao mesmo tempo à formação humanista, sensível, literária, criadora de espíritos críticos e despertos aos cuidados da vida. Assim, os resultados do estudo desta tese apontam para a retomada da ID como providência pedagógica inadiável em nível da formação do educando em todos os níveis de ensino. Por sua vez, a abordagem hermenêutica, enquanto método de aproximação ao objeto de estudo, reinstala a compreensão da formação ID do ser humano como pronúncia da historicidade e dos pré-juízos (ou juízos prévios) presentes no modo de ser finito da experiência humana, onde o conhecimento traduz o seu presente epocal levando em consideração o legado histórico e cultural das formas com que a linguagem recepciona a compreensão dos textos estudados. / This thesis represents the result of a theoretical study that aims to look into the constitution of the meanings of interdisciplinarity (ID) as revealed by Paulo Freire's and Michel Serres’s works. It also relies upon the contribution of authors, scholars and researchers that deal with ID in the sphere of Education, extending thus the dialogue between Freire and Serres to other voices, without losing the specificity of the theme in focus. Even though, in general terms, ID is a multivocal concept concerning the field of its emergence of meaning and the practical applications of its proposals, the research on the meanings it holds, both in Freire and Serres, refers us to the idea that its conception, while dialogue among disciplines, can and must be fertile in meanings and significations in relation to today’s world and for the formation of the new human: a human being at the same time scientific, responsible and sensitive to the quality of life as a whole and to the survival of the planet Earth. The conclusion herein reached is that there are common meanings in the hermeneutics of ID in the works of Freire and Serres. These are nuclear meanings that announce themselves emerging from the humanism expressed in their texts; in the formation project of the new human that moves between the scientific knowledge and the humanities, in an interdisciplinary dialogue that has for goal the emergence of the tiers-instruit (third instructed)(Serres) and of the ser mais (being plus) (Freire). This interdisciplinary resource, as recommended by the concept itself, does not nullify the disciplines, but requires them to dialogue amongst themselves in an ethically fertile perspective and consequent for the comprehension of unity in the diversity of life’s events. Besides, what is involved is a unity grounded on the understanding of the dynamics of life’s events that are, at the same time, constituents of the matter of the real and of the consciousness that we can have of it. From thence, with Freire and Serres ID acquires a proposition of emergence on the level of the human formation. To form responsible subjects, conscious of their insertion in life as a whole, refers us to the idea that education presupposes its inscription in the scientific and technical formation with definite rigors, but also and at the same time to the humanistic, sensitive, and literary formation, generative of critical minds, awakened to the cares of life. So, the results of the study of this thesis point to the recapture of ID as undelayable pedagogic measure in terms of the student's formation in all learning levels. As for the hermeneutic approach, taken as a method of approaching the object of study, it reinstalls the comprehension of the ID formation of the human being as pronunciation of the historicity and of the pre-judgements (or previous judgements/pre-concepts) embedded in the way of being finite of the human experience, where knowledge reflects its epocal present taking into account the historical and cultural legacy of the forms with which language welcomes the understanding of the studied texts.

Prostate cancer (PC) is the most common cancer in Sweden. Most patients have slow growing tumors that will not cause them any harm within their lifetime, but some have aggressive tumors and will die from their disease. The ability of current clinical practice to predict tumor behavior and disease outcome is limited leading to both over- and undertreatment of PC patients. The men who die from their disease are those that develop metastases. It is therefore of great value to find better and more sensitive prognostic techniques, so that metastatic spread can be detected (or predicted) at an early time point, and so that appropriate treatment can be offered to each subgroup of patients. The aim of this thesis was to investigate if, and by what means, highly aggressive prostate tumors influence extratumoral tissues such as the non-malignant parts of the prostate and regional lymph nodes (LN), and also if any of our findings could be of prognostic importance. Gene- and protein expression analysis were the main methods used to address these questions. Our research group has previously introduced the expression Tumor Instructed (Indicating) Normal Tissue (TINT), and we use the term TINT-changes when referring to alterations in non-malignant tissue due to the growth of a tumor nearby or elsewhere in the body. In the Dunning rat PC-model we found that MatLyLu (MLL)-tumors, having a high metastatic ability, caused pre-metastatic TINT-changes that differ from those caused by AT1-tumors who have low metastatic ability. Prostate-TINT surrounding MLL-tumors had elevated immune cell infiltration, and gene ontology enrichment analysis suggested that biological functions promoting tumor growth and metastasis were activated in MLL- while inhibited in AT1-prostate-TINT. In the regional LNs we found signs of impaired antigen presentation, and decreased quantity of T cells in the MLL-model. One of the downregulated genes in the MLL-LNs was Siglec1 (also known as Cd169), expressed by LN resident macrophages that are important for antigen presentation. When examining metastasis-free LN tissue from PC patients we found CD169 expression to be a prognostic factor for PC-specific survival, and reduced expression was linked to an increased risk of PC-specific death. Some of our findings in prostate- and LN-TINT could be seen already when the tumors were very small suggesting that differences in TINT-changes between tumors with different metastatic capability can be detected early in tumor progression. However, before coming of use in the clinic more research is needed to better define a suitable panel of prognostic TINT-factors as well as the right time window of when to use them. / Populärvetenskaplig sammanfattning Prostatacancer är den i särklass vanligaste cancerformen hos män i Sverige. De flesta patienter har en mycket långsamt växande tumör som inte orsakar dem några större besvär under deras livstid, men enbart i Sverige dör ca 2500 patienter/år av sjukdomen. Det är först vid uppkomst av metastaser som sjukdomen blir dödlig. Befintliga diagnos- och prognosmetoder är otillräckliga när det gäller att uppskatta och förutse tumörens aggressivitet och risk för att bilda metastaser. Detta gör att vissa patienter inte får tillräcklig behandling eller behandlas försent medan andra behandlas i onödan. Behovet av förbättrad diagnostik är därför stort. Om vi kan hitta markörer för potentiellt metastaserande sjukdom, och i bästa fall också behandla innan metastaser uppstår, skulle det förbättra chansen för överlevnad markant. För att kunna växa och spridas behöver en tumör inte bara förbereda närliggande vävnader utan förmodligen hela kroppen. Vår hypotes är att potentiell dödliga tumörer sannolikt är bättre på detta än mer ofarliga. Man vet från studier av andra cancerformer att farliga tumörer orsakar förändringar i det organ dit cancern senare sprids. Dessa förändringar sker för att de tumörceller som senare anländer ska kunna överleva, och processen har fått namnet pre-metastatisk nisch. Bl.a. har man sett att immunsystemet hämmas och nybildning av kärl ökar. Det är vanligt att metastaser uppstår i närliggande lymfkörtlar innan uppkomst av metastaser i andra organ. Dock är väldigt lite känt om pre-metastatiska förändringar i lymfkörtlar eftersom den forskning som hittills är gjord främst har tittat på andra organ. Inom prostatacancer finns det förvånande få studier av premetastatiska nischer överhuvudtaget, och man vet därför inte om de alls förekommer eller vilka förändringar som i så fall sker. Vår grupp har tidigare myntat uttrycket TINT som står för Tumor Instructed (Indicating) Normal Tissue (TINT är ett engelskt verb som betyder färga) och syftar på förändringar i normal vävnad som inducerats av tumören, dvs. att tumörer färgar av sig på omgivningen. Det kan vara förändringar i normal vävnad nära tumören, som i det här fallet resten av prostatan, eller i vävnad långt ifrån tumören som till exempel regionala lymfkörtlar, lungor och benmärg. Syftet med det här avhandlingsarbetet var att undersöka TINT-förändringar inducerade av aggressiv cancer och se om dessa skiljer sig från TINT-förändringar inducerade av mindre farliga tumörer, samt att utvärdera om någon TINT-förändring skulle kunna användas för att prognostisera vilka patienter som har hög risk att få metastaser. Vi har använt oss av en prostatacancer-modell i råtta där vi analyserat genoch proteinuttryck i pre-metastatiska regionala lymfkörtlar, tumörer och prostata-TINT (dvs. prostatavävnad utanför tumören). TINT-förändringar inducerade av MatLyLu (MLL), en tumör med hög metastaserande förmåga, jämfördes mot TINT-förändringar inducerade av AT1, en snabbväxande tumör men med låg förmåga att bilda metastaser. Vi kunde vi se flera skillnader mellan modellerna. Genuttrycket i MLL-prostata-TINT indikerade en aktivering av cellulära funktioner som visat sig stimulera tumörväxt och spridning såsom celldelning, viabilitet, migration, invasion, och angiogenes (nybildning av kärl). I AT1-prostata-TINT var genuttrycket kopplat till samma funktioner men verkade istället inhibera dessa. Genom att titta på vävnaderna i mikroskop kunde vi se att MLL-tumörer rekryterade färre T-celler (som har en viktig funktion i immunsvaret mot tumören), men istället fler makrofager och granulocyter till både tumören och prostata-TINT (dessa typer av immunceller har visats kunna hjälpa tumörer att växa och sprida sig). MLL-tumörer hade också fler blodkärl och lymfkärl strax utanför tumören. I de regionala lymfkörtlarna från djur med MLL-tumörer visade genuttrycket tecken på försämrad antigenpresentation, samt immunhämning och/eller induktion av immuntolerans. Immuntolerans innebär att immuncellen inte längre reagerar mot det specifika antigen den blivit tolerant emot. Detta är vanligt förekommande hos individer med cancer och är ett sätt för tumören att undkomma immunförsvaret. I vävnadsprover av lymfkörtlarna kunde vi se färre antigenpresenterande celler, och liksom i tumörerna fanns det färre T-celler i MLL-modellen, något vi kunde se redan när tumörerna var väldigt små. CD169 är ett protein som bl.a. uttrycks av sinus-makrofager i lymfkörtlar. Dessa makrofager har en central funktion i att aktivera ett tumör-specifikt immunsvar. I råttmodellen kunde vi se att regionala lymfkörtlar från djur med MLL-tumörer hade lägre nivåer av CD169 än regionala lymfkörtlar från djur med AT1-tumörer, och då antalet sinus-makrofager visat sig ha prognostiskt värde i t.ex. tjocktarmscancer, ville vi se om det kunde vara så även i prostatacancer. Därför kvantifierade vi uttrycket av CD169 i metastasfria regionala lymfkörtlar från prostatacancerpatienter och såg att låga nivåer av CD169 medförde en ökad risk för att dö i prostatacancer. Sammantaget tyder resultaten på att MLL-tumören jämfört med AT1- tumören bättre lyckas förbereda omgivande vävnad för att gynna tumörväxt och spridning, både lokalt i prostatan men också längre bort från tumören i de regionala lymfkörtlarna. Våra fynd stämmer väl överens med aktuell tumörbiologisk forskning om hur tumörer påverkar sin omgivning. Något som inte visats tidigare är att miljön utanför tumören verkar skilja sig drastiskt beroende på tumörens metastaserande förmåga, samt att dessa skillnader går att se relativt tidigt under sjukdomsförloppet och förmodligen även långt bort från tumören. Vi har också visat att särskilt aggressiv prostatacancer verkar inducera en pre-metastatisk nisch i tumördränerande lymfkörtlar likt det som beskrivits i andra modellsystem och i andra cancertyper, men hittills inte i prostatacancer. Fler studier behövs för att bättre karaktärisera de förändringar som en potentiellt dödlig prostatacancer orsakar i andra vävnader, och för att ta reda på hur denna kunskap kan användas för att förbättra diagnostik och behandling.

No description available.