WFRF:(Ling Agnes 1976 )
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- Ling, Agnes,1976-Umeå universitet,Patologi (författare)
The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
- 2015-10-28
- John Wiley & Sons,2016
- electronicrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:umu-121095
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-121095URI
- https://doi.org/10.1002/cjp2.31DOI
Kompletterande språkuppgifter
- Språk:engelska
- Sammanfattning på:engelska
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- SwePubSwePub
Klassifikation
Anmärkningar
- Ytterligare finansiärer:Cancer Research Foundation in Northern Sweden (LP 12-1959 SE)Syskonen Svenssons Foundation for Medical Research (2014 SE)
- Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T-bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype-high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1-attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T-bet may be a valuable marker in the clinical setting. Our results also indicate that T-bet is of value when analysed in molecular subgroups of CRC, allowing identification of patients with especially poor prognosis who are in need of extended treatment.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
- colorectal cancer
- Th1 lymphocytes
- intratumoural subsites
- molecular subgroups
- BRAF
- KRAS
- prognosis
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Lundberg, Ida V.Umeå universitet,Patologi(Swepub:umu)idlu0006 (författare)
- Eklöf, VincyUmeå universitet,Patologi(Swepub:umu)viyekf03 (författare)
- Wikberg, Maria L.Umeå universitet,Patologi(Swepub:umu)mahe0061 (författare)
- Öberg, ÅkeUmeå universitet,Kirurgi (författare)
- Edin, SofiaUmeå universitet,Patologi(Swepub:umu)soed0001 (författare)
- Palmqvist, RichardUmeå universitet,Patologi(Swepub:umu)ripa0001 (författare)
- Umeå universitetPatologi (creator_code:org_t)
Sammanhörande titlar
- Ingår i:The Journal of Pathology: Clinical Research: John Wiley & Sons2:1, s. 21-312056-4538
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- The Journal of Pathology: Clinical Research (Sök värdpublikationen i LIBRIS)
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