Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer

Frontiers in Immunology

Andrew T. Chan¹  Marios Giannakis³  Shuji Ogino⁴  Juha P. Väyrynen⁵  Kana Wu⁶  Xuehong Zhang⁶  Tomotaka Ugai⁸  Naohiko Akimoto⁹  Jeffrey A. Meyerhardt^1,10  Mingyang Song^1,12  Mai Chan Lau^1,13  Kota Arima^1,13  Tyler S. Twombly^1,13  Junko Kishikawa^1,13  Koichiro Haruki^1,13  Jonathan A. Nowak^1,13  Melissa Zhao^1,13  Yasutoshi Takashima^1,13  Jennifer Borowsky^1,13  Rong Zhong^1,13  Kenji Fujiyoshi^1,13 

[1] 0Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States;1Broad Institute of MIT and Harvard, Cambridge, MA, United States;2Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States;3Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, United States;Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland;Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States;Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States;Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan;Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States;Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States;Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States;Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States;

关键词: cancer-associated fibroblast (CAF);    clinical outcomes;    host–tumor interaction;    lymphocytic reaction;    microsatellite instability;    molecular pathological epidemiology (MPE);   

DOI  :  10.3389/fimmu.2022.840198

来源: DOAJ

【 摘 要 】

BackgroundThe relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized.MethodsIn 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias.ResultsImmature desmoplastic reaction was associated with lower densities of intraepithelial CD3+CD8+CD45RO+ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29–0.62; Ptrend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28–0.70; Ptrend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3+CD8+CD45RO+ cells (Ptrend <0.0001) and stromal M1-like macrophages (Ptrend = 0.0007)] and for keloid-like collagen bundles (Ptrend <0.0001 for intraepithelial CD3+CD8+CD45RO+ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23–0.44; Ptrend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16–0.39; Ptrend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05–0.28; Ptrend <0.0001) for absent (vs. marked) keloid-like collagen bundles.ConclusionsImmature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.

【 授权许可】

Unknown