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Prognostic Interact...
Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer
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- Herrera, M (author)
- Karolinska Institutet
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Mezheyeuski, A (author)
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- Villabona, L (author)
- Karolinska Institutet
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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, G (author)
- Karolinska Institutet
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Sjoblom, T (author)
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- Ostman, A (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-11-03
- 2020
- English.
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
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https://www.mdpi.com...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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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.
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cancers
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To the university's database
- By the author/editor
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Herrera, M
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Mezheyeuski, A
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Villabona, L
-
Corvigno, S
-
Strell, C
-
Klein, C
-
show more...
-
Holzlwimmer, G
-
Glimelius, B
-
Masucci, G
-
Sjoblom, T
-
Ostman, A
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show less...
- Articles in the publication
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Cancers
- By the university
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Karolinska Institutet