Ugai, T., Shimizu, T., Kawamura, H., Ugai, S., Takashima, Y., Usui, G., Väyrynen, J.P., Okadome, K., Haruki, K., Akimoto, N., Masugi, Y., da Silva, A., Mima, K., Zhang, X., Chan, A.T., Wang, M., Garrett, W.S., Freeman, G.J., Meyerhardt, J.A., Nowak, J.A., Song, M., Giannakis, M. and Ogino, S. (2023), Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma. Clin Transl Immunol, 12: e1453. https://doi.org/10.1002/cti2.1453
Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma
|Author:||Ugai, Tomotaka1,2; Shimizu, Takashi1; Kawamura, Hidetaka1;|
1Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
3Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
4Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
6Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
7Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
8Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
9Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
10Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
11Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
12Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
13Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA
14Harvard T.H. Chan Microbiome in Public Health Center, Boston, MA, USA
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
16Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
17Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA
|Online Access:||PDF Full Text (PDF, 5.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20231011139733
John Wiley & Sons,
|Publish Date:|| 2023-10-11
Objectives: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma.
Methods: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations.
Results: Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41–1.51), 0.64 (0.32–1.28) and 0.50 (0.25–0.99), respectively (Ptrend = 0.032).
Conclusions: Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.
Clinical & translational immunology
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by US National Institutes of Health (NIH) grants (P01 CA87969 to Meir J Stampfer; UM1 CA186107 to Meir J Stampfer; P01 CA55075 to Walter C Willett; UM1 CA167552 to Walter C Willett; U01 CA167552 to Lorelei A Mucci and Walter C Willett; P50 CA127003 to CSF; R01 CA118553 to CSF; R01 CA169141 to CSF; R01 CA137178 to ATC; K24 DK098311 to ATC; R01 CA248857 to SO; R35 CA197735 to SO; R01 CA151993 to SO; R00 CA215314 to MS; and K07 CA188126 to XZ; R21 CA252962 to XZ); by Cancer Research UK Grand Challenge Award (UK C10674/A27140 to MG and SO); by Nodal Award (2016-02) from the Dana-Farber Harvard Cancer Center (to SO); by the Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17 to CSF and MG), administered by the American Association for Cancer Research, a scientific partner of SU2C; by the American Cancer Society Mentored Research Scholar Grant (MRSG-17-220-01-NEC to MS); by the American Cancer Society Research Scholar Grant (131040-RSG-17-190-01-NEC to XZ); 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. TU was supported by grants from Japan Society for the Promotion of Science (201960541), Prevent Cancer Foundation, and Harvey V. Fineberg Fellowship in Cancer Prevention. HK, KH, TS and TU were supported by fellowship grants from the Uehara Memorial Foundation. KH was supported by the Mitsukoshi Health and Welfare Foundation. TS was supported by the Mochida Memorial Foundation and the Fukuda Memorial Foundation. ATC is a Stuart and Suzanne Steele MGH Research Scholar. JAM's research is supported by the Douglas Gray Woodruff Chair fund, the Guo Shu Shi Fund, Anonymous Family Fund for Innovations in Colorectal Cancer, P Fund, and the George Stone Family Foundation. 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 the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.
© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.