Akimoto N, Väyrynen JP, Zhao M, Ugai T, Fujiyoshi K, Borowsky J, Zhong R, Haruki K, Arima K, Lau MC, Kishikawa J, Twombly TS, Takashima Y, Song M, Zhang X, Wu K, Chan AT, Meyerhardt JA, Giannakis M, Nowak JA and Ogino S (2022) Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer. Front. Immunol. 13:840198. doi: 10.3389/fimmu.2022.840198
Desmoplastic reaction, immune cell response, and prognosis in colorectal cancer
|Author:||Akimoto, Naohiko1,2; Väyrynen, Juha P.1,3,4; Zhao, Melissa1;|
1Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
2Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
3Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
4Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
5Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
7Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
8Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United States
9Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
10Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States
11Broad Institute of MIT and Harvard, Cambridge, MA, United States
12Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
13Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, United States
|Online Access:||PDF Full Text (PDF, 8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022092660063
|Publish Date:|| 2022-09-26
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; 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.
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.
Frontiers in immunology
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by the U.S. National Institutes of Health (NIH) grants (P01 CA87969; UM1 CA186107; P01 CA55075; UM1 CA167552; U01 CA167552; R35 CA253185 to AC; R35 CA197735 to SO; R01 CA151993 to SO; R01 CA248857 to SO); by Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17 to MG), administered by the American Association for Cancer Research, a scientific partner of SU2C; and by grants from the Project P Fund, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance and SU2C. XZ was supported by the American Cancer Society Research Scholar Grant (RSG NEC-130476). KF was supported by fellowship grants from the Uehara Memorial Foundation and Grant of The Clinical Research Promotion Foundation (2018). RZ was supported by a fellowship grant from Huazhong University of Science and Technology. KA and TU were supported by a grant from Overseas Research Fellowship (201860083 to KA; 201960541 to TU) from Japan Society for the Promotion of Science. KH was supported by fellowship grants from the Uehara Memorial Foundation and the Mitsukoshi Health and Welfare Foundation. AC is a Stuart and Suzanne Steele MGH Research Scholar. MG is supported by an ASCO Conquer Cancer Foundation Career Development Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2022 Akimoto, Väyrynen, Zhao, Ugai, Fujiyoshi, Borowsky, Zhong, Haruki, Arima, Lau, Kishikawa, Twombly, Takashima, Song, Zhang, Wu, Chan, Meyerhardt, Giannakis, Nowak and Ogino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.