Frontiers in Immunology (Mar 2022)
Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer
- Naohiko Akimoto,
- Naohiko Akimoto,
- Juha P. Väyrynen,
- Juha P. Väyrynen,
- Juha P. Väyrynen,
- Melissa Zhao,
- Tomotaka Ugai,
- Tomotaka Ugai,
- Kenji Fujiyoshi,
- Jennifer Borowsky,
- Rong Zhong,
- Koichiro Haruki,
- Kota Arima,
- Mai Chan Lau,
- Junko Kishikawa,
- Tyler S. Twombly,
- Yasutoshi Takashima,
- Mingyang Song,
- Mingyang Song,
- Mingyang Song,
- Xuehong Zhang,
- Xuehong Zhang,
- Kana Wu,
- Kana Wu,
- Kana Wu,
- Andrew T. Chan,
- Andrew T. Chan,
- Andrew T. Chan,
- Andrew T. Chan,
- Jeffrey A. Meyerhardt,
- Marios Giannakis,
- Marios Giannakis,
- Marios Giannakis,
- Jonathan A. Nowak,
- Shuji Ogino,
- Shuji Ogino,
- Shuji Ogino,
- Shuji Ogino
Affiliations
- Naohiko Akimoto
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Naohiko Akimoto
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
- Juha P. Väyrynen
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Juha P. Väyrynen
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- Juha P. Väyrynen
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
- Melissa Zhao
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Tomotaka Ugai
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Tomotaka Ugai
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Kenji Fujiyoshi
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Jennifer Borowsky
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Rong Zhong
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Koichiro Haruki
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Kota Arima
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Mai Chan Lau
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Junko Kishikawa
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Tyler S. Twombly
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Yasutoshi Takashima
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Mingyang Song
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States
- Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Kana Wu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Kana Wu
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States
- Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Andrew T. Chan
- 0Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Jeffrey A. Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- Marios Giannakis
- 1Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Marios Giannakis
- 2Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Jonathan A. Nowak
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Shuji Ogino
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Shuji Ogino
- 1Broad Institute of MIT and Harvard, Cambridge, MA, United States
- Shuji Ogino
- 3Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2022.840198
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- cancer-associated fibroblast (CAF)
- clinical outcomes
- host–tumor interaction
- lymphocytic reaction
- microsatellite instability
- molecular pathological epidemiology (MPE)
