Статья

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

Naohiko AkimotoDepartment of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, JapanJuha P. VäyrynenCancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandMelissa ZhaoProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesTomotaka UgaiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesKenji FujiyoshiProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesJennifer BorowskyProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesRong ZhongProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesKoichiro HarukiProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesKota ArimaProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesMai Chan LauProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesJunko KishikawaProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesTyler S. TwomblyProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesYasutoshi TakashimaProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesMingyang SongClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesXuehong ZhangChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesKana WuChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesAndrew T. ChanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesJeffrey A. MeyerhardtDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United StatesMarios GiannakisBroad Institute of MIT and Harvard, Cambridge, MA, United StatesJonathan A. NowakProgram in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United StatesShuji OginoBroad Institute of MIT and Harvard, Cambridge, MA, United States

2022en

ABI

Аннотация

Background The 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. Methods In 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. Results Immature 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; P trend &lt;0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28–0.70; P trend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3 + CD8 + CD45RO + cells (P trend &lt;0.0001) and stromal M1-like macrophages (P trend = 0.0007)] and for keloid-like collagen bundles (P trend &lt;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; P trend &lt;0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16–0.39; P trend &lt;0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05–0.28; P trend &lt;0.0001) for absent (vs. marked) keloid-like collagen bundles. Conclusions Immature 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.

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Идентификаторы

DOI: 10.3389/fimmu.2022.840198

Цитирования и источники

Цитирований: 2Использованных источников: 0

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