Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer

Cancers

Sara Corvigno¹  Tobias Sjöblom²  Carina Strell²  Artur Mezheyeuski²  Bengt Glimelius²  Mercedes Herrera³  Arne Östman³  Lisa Villabona³  Giuseppe Masucci³  Gabriele Hölzlwimmer⁴  Christian Klein⁵ 

[1] Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden;Oncology and Pathology Department, Karolinska Institutet, 17164 Stockholm, Sweden;Roche Innovation Center Munich, Department of Pathology and Tissue Analytics, Roche Pharma Research and Early Development pRED, 82377 Penzberg, Germany;Roche Innovation Center Zurich, Roche Pharma Research and Early Development pRED, 8952 Schlieren, Switzerland;

关键词: colon cancer;    tumor microenvironment;    cancer associated fibroblasts;    T lymphocytes;    prognosis;   

DOI  :  10.3390/cancers12113238

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown