Open AccessPrognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer
Author(s) -
Mercedes Herrera,
Artur Mezheyeuski,
Lisa Villabona,
Sara Corvigno,
Carina Strell,
Christian Klein,
Gabriele Hölzlwimmer,
Bengt Glimelius,
Giuseppe Masucci,
Tobias Sjöblom,
Arne Östman
Publication year - 2020
Publication title -
cancers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.818
H-Index - 76
ISSN - 2072-6694
DOI - 10.3390/cancers12113238
Subject(s) - immune system , foxp3 , colorectal cancer , stromal cell , medicine , cd8 , fibroblast , oncology , cohort , cancer research , cancer associated fibroblasts , tumor microenvironment , cancer , immunology , biology , cell culture , genetics
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.