TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas
Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL)...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1442999 |
| _version_ | 1818288028975628288 |
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| author | Tsuyoshi Hamada Thing Rinda Soong Yohei Masugi Keisuke Kosumi Jonathan A. Nowak Annacarolina da Silva Xinmeng Jasmine Mu Tyler S. Twombly Hideo Koh Juhong Yang Mingyang Song Li Liu Mancang Gu Yan Shi Katsuhiko Nosho Teppei Morikawa Kentaro Inamura Sachet A. Shukla Catherine J. Wu Levi A. Garraway Xuehong Zhang Kana Wu Jeffrey A. Meyerhardt Andrew T. Chan Jonathan N. Glickman Scott J. Rodig Gordon J. Freeman Charles S. Fuchs Reiko Nishihara Marios Giannakis Shuji Ogino |
| author_facet | Tsuyoshi Hamada Thing Rinda Soong Yohei Masugi Keisuke Kosumi Jonathan A. Nowak Annacarolina da Silva Xinmeng Jasmine Mu Tyler S. Twombly Hideo Koh Juhong Yang Mingyang Song Li Liu Mancang Gu Yan Shi Katsuhiko Nosho Teppei Morikawa Kentaro Inamura Sachet A. Shukla Catherine J. Wu Levi A. Garraway Xuehong Zhang Kana Wu Jeffrey A. Meyerhardt Andrew T. Chan Jonathan N. Glickman Scott J. Rodig Gordon J. Freeman Charles S. Fuchs Reiko Nishihara Marios Giannakis Shuji Ogino |
| author_sort | Tsuyoshi Hamada |
| collection | DOAJ |
| description | Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response to immunotherapy. It remains to be determined clinical, pathological, and molecular features of TIME subtypes of colorectal cancer. Using 812 colon and rectal carcinoma cases from the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association of tumor characteristics and survival outcomes with four TIME subtypes (TIME 1, CD274low/TILabsent; TIME 2, CD274high/TILpresent; TIME 3, CD274low/TILpresent; and TIME 4, CD274high/TILabsent). In survival analyses, Cox proportional hazards models were adjusted for potential confounders, including microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutation status. TIME subtypes 1, 2, 3 and 4 had 218 (27%), 117 (14%), 103 (13%), and 374 (46%) colorectal cancer cases, respectively. Compared with TIL-absent subtypes (TIME 1 and 4), TIL-present subtypes (TIME 2 and 3) were associated with high-level MSI, high-degree CIMP, BRAF mutation, and higher amounts of neoantigens (p < 0.001). TIME subtypes were not significantly associated with colorectal cancer-specific or overall survival. In conclusion, TIL-present TIME subtypes of colorectal cancer are associated with high levels of MSI and neoantigen load, supporting better responsiveness to cancer immunotherapy. Further studies examining tumor molecular alterations and additional factors in the tumor microenvironment may inform development of immunoprevention and immunotherapy strategies. |
| first_indexed | 2024-12-13T01:49:53Z |
| format | Article |
| id | doaj.art-63ee06ae114e4a4fba2cde1620b7523b |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T01:49:53Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-63ee06ae114e4a4fba2cde1620b7523b2022-12-22T00:03:33ZengTaylor & Francis GroupOncoImmunology2162-402X2018-07-017710.1080/2162402X.2018.14429991442999TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomasTsuyoshi Hamada0Thing Rinda Soong1Yohei Masugi2Keisuke Kosumi3Jonathan A. Nowak4Annacarolina da Silva5Xinmeng Jasmine Mu6Tyler S. Twombly7Hideo Koh8Juhong Yang9Mingyang Song10Li Liu11Mancang Gu12Yan Shi13Katsuhiko Nosho14Teppei Morikawa15Kentaro Inamura16Sachet A. Shukla17Catherine J. Wu18Levi A. Garraway19Xuehong Zhang20Kana Wu21Jeffrey A. Meyerhardt22Andrew T. Chan23Jonathan N. Glickman24Scott J. Rodig25Gordon J. Freeman26Charles S. Fuchs27Reiko Nishihara28Marios Giannakis29Shuji Ogino30Dana-Farber Cancer Institute and Harvard Medical SchoolBrigham and Women's Hospital and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolBrigham and Women's Hospital and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolMassachusetts General Hospital and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolRheumatology, and Clinical Immunology, Sapporo Medical University School of MedicineGraduate School of Medicine, The University of TokyoJapanese Foundation for Cancer ResearchDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolBrigham and Women's Hospital and Harvard Medical SchoolHarvard T.H. Chan School of Public HealthDana-Farber Cancer Institute and Harvard Medical SchoolMassachusetts General Hospital and Harvard Medical SchoolBeth Israel Deaconess Medical CenterDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolYale Cancer CenterDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolDana-Farber Cancer Institute and Harvard Medical SchoolInhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response to immunotherapy. It remains to be determined clinical, pathological, and molecular features of TIME subtypes of colorectal cancer. Using 812 colon and rectal carcinoma cases from the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association of tumor characteristics and survival outcomes with four TIME subtypes (TIME 1, CD274low/TILabsent; TIME 2, CD274high/TILpresent; TIME 3, CD274low/TILpresent; and TIME 4, CD274high/TILabsent). In survival analyses, Cox proportional hazards models were adjusted for potential confounders, including microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutation status. TIME subtypes 1, 2, 3 and 4 had 218 (27%), 117 (14%), 103 (13%), and 374 (46%) colorectal cancer cases, respectively. Compared with TIL-absent subtypes (TIME 1 and 4), TIL-present subtypes (TIME 2 and 3) were associated with high-level MSI, high-degree CIMP, BRAF mutation, and higher amounts of neoantigens (p < 0.001). TIME subtypes were not significantly associated with colorectal cancer-specific or overall survival. In conclusion, TIL-present TIME subtypes of colorectal cancer are associated with high levels of MSI and neoantigen load, supporting better responsiveness to cancer immunotherapy. Further studies examining tumor molecular alterations and additional factors in the tumor microenvironment may inform development of immunoprevention and immunotherapy strategies.http://dx.doi.org/10.1080/2162402X.2018.1442999adaptive immunitybiomarkerscohort studiescolorectal neoplasmsimmunologyimmunotherapymolecular pathological epidemiologysurvival analysist-lymphocytestumor microenvironment |
| spellingShingle | Tsuyoshi Hamada Thing Rinda Soong Yohei Masugi Keisuke Kosumi Jonathan A. Nowak Annacarolina da Silva Xinmeng Jasmine Mu Tyler S. Twombly Hideo Koh Juhong Yang Mingyang Song Li Liu Mancang Gu Yan Shi Katsuhiko Nosho Teppei Morikawa Kentaro Inamura Sachet A. Shukla Catherine J. Wu Levi A. Garraway Xuehong Zhang Kana Wu Jeffrey A. Meyerhardt Andrew T. Chan Jonathan N. Glickman Scott J. Rodig Gordon J. Freeman Charles S. Fuchs Reiko Nishihara Marios Giannakis Shuji Ogino TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas OncoImmunology adaptive immunity biomarkers cohort studies colorectal neoplasms immunology immunotherapy molecular pathological epidemiology survival analysis t-lymphocytes tumor microenvironment |
| title | TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas |
| title_full | TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas |
| title_fullStr | TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas |
| title_full_unstemmed | TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas |
| title_short | TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas |
| title_sort | time tumor immunity in the microenvironment classification based on tumor cd274 pd l1 expression status and tumor infiltrating lymphocytes in colorectal carcinomas |
| topic | adaptive immunity biomarkers cohort studies colorectal neoplasms immunology immunotherapy molecular pathological epidemiology survival analysis t-lymphocytes tumor microenvironment |
| url | http://dx.doi.org/10.1080/2162402X.2018.1442999 |
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