Tomotaka Ugai, Takashi Shimizu, Hidetaka Kawamura, Satoko Ugai, Yasutoshi Takashima, Genki Usui, Juha P V?yrynen, Kazuo Okadome, Koichiro Haruki, Naohiko Akimoto, Yohei Masugi, Annacarolina da Silva, 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
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We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of <i>F. nucleatum</i> in colorectal carcinoma.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We assessed tumor CD274 expression by immunohistochemistry and <i>F. nucleatum</i> 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 <i>KRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> mutations.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>Fusobacterium nucleatum</i> DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue (<i>P</i> = 0.0077). For one category-unit increase in three ordinal <i>F. nucleatum</i> 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 (<i>P</i><sub>trend</sub> = 0.032).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor <i>F. nucleatum</i> enrichment) tend to be used by different tumor subgroups.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1453","citationCount":"0","resultStr":"{\"title\":\"Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma\",\"authors\":\"Tomotaka Ugai, Takashi Shimizu, Hidetaka Kawamura, Satoko Ugai, Yasutoshi Takashima, Genki Usui, Juha P V?yrynen, Kazuo Okadome, Koichiro Haruki, Naohiko Akimoto, Yohei Masugi, Annacarolina da Silva, 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\",\"doi\":\"10.1002/cti2.1453\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>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 <i>Fusobacterium nucleatum</i>. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of <i>F. nucleatum</i> in colorectal carcinoma.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We assessed tumor CD274 expression by immunohistochemistry and <i>F. nucleatum</i> 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 <i>KRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> mutations.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p><i>Fusobacterium nucleatum</i> DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue (<i>P</i> = 0.0077). For one category-unit increase in three ordinal <i>F. nucleatum</i> 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 (<i>P</i><sub>trend</sub> = 0.032).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor <i>F. nucleatum</i> enrichment) tend to be used by different tumor subgroups.</p>\\n </section>\\n </div>\",\"PeriodicalId\":152,\"journal\":{\"name\":\"Clinical & Translational Immunology\",\"volume\":\"12 8\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1453\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Translational Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1453\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1453","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma
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.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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