The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer

Kolorektaalisyöpä on maailmanlaajuisesti yksi yleisimmistä ja kuolettavimmista syövistä. Immuunisolujen rooli sen kehityksessä on tunnettu jo pitkään. Korkea sytotoksisten T-solujen tiheys primäärikasvaimessa on yhdistetty parempaan kolorektaalisyövän ennusteeseen, mutta B-solulinjan ennustemerkitys...

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Päätekijä: Sirkiä, Onni
Muut tekijät: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Aineistotyyppi: Pro gradu
Kieli:eng
Julkaistu: 2022
Aiheet:
Linkit: https://jyx.jyu.fi/handle/123456789/81952
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author Sirkiä, Onni
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Sirkiä, Onni Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Sirkiä, Onni Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Sirkiä, Onni
datasource_str_mv jyx
description Kolorektaalisyöpä on maailmanlaajuisesti yksi yleisimmistä ja kuolettavimmista syövistä. Immuunisolujen rooli sen kehityksessä on tunnettu jo pitkään. Korkea sytotoksisten T-solujen tiheys primäärikasvaimessa on yhdistetty parempaan kolorektaalisyövän ennusteeseen, mutta B-solulinjan ennustemerkitys tunnetaan huonommin. Tämän tutkielman tarkoitus oli kartoittaa B-solujen ja plasmasolujen eri alatyyppien esiintymistä kolorektaalisyöpäkasvaimissa sekä arvioida niiden ennustemerkitystä. Kudosmikrosirunäytteet 912 primäärikasvaimesta immuno-värjättiin B-solujen ja plasmasolujen eri alatyyppien solumerkkiaineilla multiplex-immunohistokemian avulla. QuPath-ohjelmalla tehdyn koneoppimispohjaisen kuva-analyysin tulosten perusteella näytteistä havaitut B- ja plasmasolut jaettiin alatyypeikseen, ja kasvainten solutiheydet laskettiin erikseen kullekin alatyypille. Eri alatyyppien ennustemerkityksiä tarkasteltiin sekä Kaplan-Meierin menetelmän että Coxin regressioiden avulla. Tulosten perusteella korkea plasmasolutiheys on yhteydessä parempaan kolorektaalisyövän ennusteeseen solujen alatyypistä sekä muista tekijöistä riippumatta. Havainto on ristiriidassa IgG1+ plasmasolujen hypotisoidun paremman ennustemerkityksen kanssa. B-muistisolujen ja antigeeniä esittelevien B-solujen korkea tiheys invaasiorintaman näytteissä oli yhteydessä parempaan ennusteeseen, kun taas kasvaimen keskiosan näytteissä merkittävin ennustetekijä B-solujen osalta oli korkea naiivien B-solujen solutiheys. B-solujen ennustemerkitys oli kuitenkin riippuvainen muista tekijöistä, mikä viittaa niiden toimivan yhteistyössä todennäköisesti sytotoksisten T-lymfosyyttien kanssa. Colorectal cancer is one of the most common and deadly cancers worldwide. The significance of immune cells in colorectal tumor development is well recognized. High density of cytotoxic T cells in colorectal tumors has been associated with a better prognosis, but the prognostic importance of B lymphocyte lineage is less well understood. The aim of this study was to assess the presence of different B cell and plasma cell subsets in colorectal tumors and evaluate their prognostic importance. Tissue microarray samples from 912 primary colorectal tumors were stained with antibodies against different B cell and plasma cell markers by using multiplex immunohistochemistry. Images of the immunostained tumor tissue samples were analyzed with machine learning-based image analysis software QuPath. Detected cells were phenotyped based on the intensity of different surface markers, and cell densities were calculated for all the observed subsets. The prognostic importance of different plasma cell and B cell subsets was assessed using Kaplan-Meier estimators and Cox regression analyses. High plasma cell density had independent association with better survival regardless of the subset, thus contradicting the hypothesized superior prognostic potential of IgG1+ plasma cells. High densities of memory and antigen-presenting B cells were associated with better survival in the invasive margin, whereas high density of naïve B cells showed association with improved survival in the tumor center. However, the prognostic importance of B cells was not independent, suggesting that they may cooperate with cytotoxic T lymphocytes.
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Immuunisolujen rooli sen kehityksess\u00e4 on tunnettu jo pitk\u00e4\u00e4n. Korkea sytotoksisten T-solujen tiheys prim\u00e4\u00e4rikasvaimessa on yhdistetty parempaan kolorektaalisy\u00f6v\u00e4n ennusteeseen, mutta B-solulinjan ennustemerkitys tunnetaan huonommin. T\u00e4m\u00e4n tutkielman tarkoitus oli kartoittaa B-solujen ja plasmasolujen eri alatyyppien esiintymist\u00e4 kolorektaalisy\u00f6p\u00e4kasvaimissa sek\u00e4 arvioida niiden ennustemerkityst\u00e4. Kudosmikrosirun\u00e4ytteet 912 prim\u00e4\u00e4rikasvaimesta immuno-v\u00e4rj\u00e4ttiin B-solujen ja plasmasolujen eri alatyyppien solumerkkiaineilla multiplex-immunohistokemian avulla. QuPath-ohjelmalla tehdyn koneoppimispohjaisen kuva-analyysin tulosten perusteella n\u00e4ytteist\u00e4 havaitut B- ja plasmasolut jaettiin alatyypeikseen, ja kasvainten solutiheydet laskettiin erikseen kullekin alatyypille. 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spellingShingle Sirkiä, Onni The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer humoral immunity tumor microenvironment Solu- ja molekyylibiologia Cell and molecular biology 4013 solubiologia immunohistokemia lymfosyytit cell biology immunohistochemistry lymphocytes
title The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
title_full The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
title_fullStr The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
title_full_unstemmed The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
title_short The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
title_sort prognostic importance of b cells and plasma cells in colorectal cancer
title_txtP The Prognostic Importance of B Cells and Plasma Cells in Colorectal Cancer
topic humoral immunity tumor microenvironment Solu- ja molekyylibiologia Cell and molecular biology 4013 solubiologia immunohistokemia lymfosyytit cell biology immunohistochemistry lymphocytes
topic_facet 4013 Cell and molecular biology Solu- ja molekyylibiologia cell biology humoral immunity immunohistochemistry immunohistokemia lymfosyytit lymphocytes solubiologia tumor microenvironment
url https://jyx.jyu.fi/handle/123456789/81952 http://www.urn.fi/URN:NBN:fi:jyu-202206223557
work_keys_str_mv AT sirkiäonni prognosticimportanceofbcellsandplasmacellsincolorectalcancer AT sirkiäonni theprognosticimportanceofbcellsandplasmacellsincolorectalcancer