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High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration
DC Field | Value | Language |
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dc.date.accessioned | 2023-03-10T01:33:39Z | - |
dc.date.available | 2023-03-10T01:33:39Z | - |
dc.date.issued | 2022-11 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193225 | - |
dc.description.abstract | Background: Relationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated. Methods: Forty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis. For validation, formalin-fixed tissues from 375 lung ADC, 118 lung squamous cell carcinoma (SqCC), 338 colon ADC, and 78 lung cancer patients treated with anti-PD-1/PD-L1 immunotherapy were immunostained for HK2, CD8, and FOXP3. Results: Based on immunoprofiling of lung ADC, HK2 tumor expression was associated with the composition of lymphoid cells rather than myeloid cells. High HK2 tumor expression was associated with immunosuppressive/pro-tumorigenic features, especially decreased ratio of CD8 + T-cells to Tregs (rho = -0.415, P = 0.012). This correlation was also confirmed in four different cohorts including lung ADC and SqCC, colon ADC, and the immunotherapy cohort (rho = -0.175~-0.335, all P < 0.05). A low CD8 + T-cell to Treg ratio was associated with poor progression-free survival and overall survival in lung SqCC patients, and a shorter overall survival in the immunotherapy cohort (all, P < 0.05). Conclusion: An increase in HK2 expression may contribute to shaping the immunosuppressive/pro-tumorigenic tumor microenvironment by modulating the CD8 + T-cell to Treg ratio. Targeting tumor HK2 expression might be a potential strategy for enhancing anti-tumor immunity. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.relation.isPartOf | BMC CANCER | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adenocarcinoma of Lung* / metabolism | - |
dc.subject.MESH | B7-H1 Antigen / metabolism | - |
dc.subject.MESH | CD8-Positive T-Lymphocytes | - |
dc.subject.MESH | Carcinogenesis / metabolism | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / pathology | - |
dc.subject.MESH | Carcinoma, Squamous Cell* / metabolism | - |
dc.subject.MESH | Formaldehyde | - |
dc.subject.MESH | Hexokinase / metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lung Neoplasms* / pathology | - |
dc.subject.MESH | Lymphocytes, Tumor-Infiltrating | - |
dc.subject.MESH | T-Lymphocytes, Regulatory | - |
dc.subject.MESH | Tumor Microenvironment | - |
dc.title | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학교실) | - |
dc.contributor.googleauthor | Sehui Kim | - |
dc.contributor.googleauthor | Jaemoon Koh | - |
dc.contributor.googleauthor | Seung Geun Song | - |
dc.contributor.googleauthor | Jeemin Yim | - |
dc.contributor.googleauthor | Miso Kim | - |
dc.contributor.googleauthor | Bhumsuk Keam | - |
dc.contributor.googleauthor | Young Tae Kim | - |
dc.contributor.googleauthor | Jihun Kim | - |
dc.contributor.googleauthor | Doo Hyun Chung | - |
dc.contributor.googleauthor | Yoon Kyung Jeon | - |
dc.identifier.doi | 10.1186/s12885-022-10239-6 | - |
dc.relation.journalcode | J00351 | - |
dc.identifier.eissn | 1471-2407 | - |
dc.identifier.pmid | 36320008 | - |
dc.subject.keyword | CD8 + T-cell to Treg ratio | - |
dc.subject.keyword | Glycolysis | - |
dc.subject.keyword | Hexokinase-2 | - |
dc.subject.keyword | Immunotherapy | - |
dc.subject.keyword | Tumor microenvironment | - |
dc.subject.keyword | Tumor-infiltrating lymphocytes | - |
dc.citation.volume | 22 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1120 | - |
dc.identifier.bibliographicCitation | BMC CANCER, Vol.22(1) : 1120, 2022-11 | - |
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