Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma
Abstract 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 ove...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Clinical & Translational Immunology |
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| Online Access: | https://doi.org/10.1002/cti2.1453 |
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| author | Tomotaka Ugai Takashi Shimizu Hidetaka Kawamura Satoko Ugai Yasutoshi Takashima Genki Usui Juha P Väyrynen Kazuo Okadome Koichiro Haruki Naohiko Akimoto Yohei Masugi Annacarolina daSilva Kosuke Mima Xuehong Zhang Andrew T Chan Molin Wang Wendy S Garrett Gordon J Freeman Jeffrey A Meyerhardt Jonathan A Nowak Mingyang Song Marios Giannakis Shuji Ogino |
| author_facet | Tomotaka Ugai Takashi Shimizu Hidetaka Kawamura Satoko Ugai Yasutoshi Takashima Genki Usui Juha P Väyrynen Kazuo Okadome Koichiro Haruki Naohiko Akimoto Yohei Masugi Annacarolina daSilva Kosuke Mima Xuehong Zhang Andrew T Chan Molin Wang Wendy S Garrett Gordon J Freeman Jeffrey A Meyerhardt Jonathan A Nowak Mingyang Song Marios Giannakis Shuji Ogino |
| author_sort | Tomotaka Ugai |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T12:30:43Z |
| format | Article |
| id | doaj.art-6d5f4ff4a6054b57bc63ecd44396a8c0 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-03-12T12:30:43Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-6d5f4ff4a6054b57bc63ecd44396a8c02023-08-29T11:16:33ZengWileyClinical & Translational Immunology2050-00682023-01-01128n/an/a10.1002/cti2.1453Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinomaTomotaka Ugai0Takashi Shimizu1Hidetaka Kawamura2Satoko Ugai3Yasutoshi Takashima4Genki Usui5Juha P Väyrynen6Kazuo Okadome7Koichiro Haruki8Naohiko Akimoto9Yohei Masugi10Annacarolina daSilva11Kosuke Mima12Xuehong Zhang13Andrew T Chan14Molin Wang15Wendy S Garrett16Gordon J Freeman17Jeffrey A Meyerhardt18Jonathan A Nowak19Mingyang Song20Marios Giannakis21Shuji Ogino22Program in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USADepartment of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USADepartment of Pathology and Laboratory Medicine Weill Cornell Medicine New York NY USADepartment of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University Kumamoto JapanChanning Division of Network Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USAChanning Division of Network Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USADepartment of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USADepartment of Medical Oncology Dana‐Farber Cancer Institute and Harvard Medical School Boston MA USADepartment of Medical Oncology Dana‐Farber Cancer Institute and Harvard Medical School Boston MA USADepartment of Medical Oncology Dana‐Farber Cancer Institute and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USADepartment of Nutrition Harvard T.H. Chan School of Public Health Boston MA USADepartment of Medical Oncology Dana‐Farber Cancer Institute and Harvard Medical School Boston MA USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USAAbstract 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.https://doi.org/10.1002/cti2.1453colorectal neoplasmimmune toleranceimmunologymicrobiologymolecular pathological epidemiology |
| spellingShingle | Tomotaka Ugai Takashi Shimizu Hidetaka Kawamura Satoko Ugai Yasutoshi Takashima Genki Usui Juha P Väyrynen Kazuo Okadome Koichiro Haruki Naohiko Akimoto Yohei Masugi Annacarolina daSilva Kosuke Mima Xuehong Zhang Andrew T Chan Molin Wang Wendy S Garrett Gordon J Freeman Jeffrey A Meyerhardt Jonathan A Nowak Mingyang Song Marios Giannakis Shuji Ogino Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma Clinical & Translational Immunology colorectal neoplasm immune tolerance immunology microbiology molecular pathological epidemiology |
| title | Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma |
| title_full | Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma |
| title_fullStr | Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma |
| title_full_unstemmed | Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma |
| title_short | Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD‐L1) expression in colorectal carcinoma |
| title_sort | inverse relationship between fusobacterium nucleatum amount and tumor cd274 pd l1 expression in colorectal carcinoma |
| topic | colorectal neoplasm immune tolerance immunology microbiology molecular pathological epidemiology |
| url | https://doi.org/10.1002/cti2.1453 |
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