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Prognostic Interact...
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Herrera, MKarolinska Institutet
(author)
Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer
- Article/chapterEnglish2020
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:145205039
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http://kipublications.ki.se/Default.aspx?queryparsed=id:145205039URI
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https://doi.org/10.3390/cancers12113238DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Inter-case variations in immune cell and fibroblast composition are associated with prognosis in solid tumors, including colon cancer. A series of experimental studies suggest immune-modulatory roles of marker-defined fibroblast populations, including FAP-positive fibroblasts. These studies imply that the fibroblast status of tumors might affect the prognostic significance of immune-related features. Analyses of a population-based colon cancer cohort demonstrated good prognosis associations of FAP intensity and CD8a density. Notably, a significant prognostic interaction was detected between these markers (p = 0.013 in nonadjusted analyses and p = 0.003 in analyses adjusted for cofounding factors) in a manner where the good prognosis association of CD8 density was restricted to the FAP intensity-high group. This prognostic interaction was also detected in an independent randomized trial-derived colon cancer cohort (p = 0.048 in nonadjusted analyses). In the CD8-high group, FAP intensity was significantly associated with a higher total tumor density of FoxP3-positive immune cells and a higher ratio of epithelial-to-stromal density of CD8a T cells. The study presents findings relevant for the ongoing efforts to improve the prognostic performance of CD8-related markers and should be followed by additional validation studies. Furthermore, findings support, in general, earlier model-derived studies implying fibroblast subsets as clinically relevant modulators of immune surveillance. Finally, the associations between FAP intensity and specific immune features suggest mechanisms of fibroblast-immune crosstalk with therapeutic potential.
Added entries (persons, corporate bodies, meetings, titles ...)
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Mezheyeuski, A
(author)
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Villabona, LKarolinska Institutet
(author)
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Corvigno, S
(author)
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Strell, C
(author)
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Klein, C
(author)
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Holzlwimmer, G
(author)
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Glimelius, B
(author)
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Masucci, GKarolinska Institutet
(author)
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Sjoblom, T
(author)
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Ostman, AKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:Cancers: MDPI AG12:112072-6694
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Cancers
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Herrera, M
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Mezheyeuski, A
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Villabona, L
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Corvigno, S
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Strell, C
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Klein, C
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show more...
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Holzlwimmer, G
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Glimelius, B
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Masucci, G
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Sjoblom, T
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Ostman, A
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Cancers
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Karolinska Institutet