High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration
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...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10239-6 |
| _version_ | 1811233660643311616 |
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| author | Sehui Kim Jaemoon Koh Seung Geun Song Jeemin Yim Miso Kim Bhumsuk Keam Young Tae Kim Jihun Kim Doo Hyun Chung Yoon Kyung Jeon |
| author_facet | Sehui Kim Jaemoon Koh Seung Geun Song Jeemin Yim Miso Kim Bhumsuk Keam Young Tae Kim Jihun Kim Doo Hyun Chung Yoon Kyung Jeon |
| author_sort | Sehui Kim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T11:23:19Z |
| format | Article |
| id | doaj.art-6a9f7692bb3948a5be19b5afa97617aa |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T11:23:19Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6a9f7692bb3948a5be19b5afa97617aa2022-12-22T03:35:17ZengBMCBMC Cancer1471-24072022-11-0122111110.1186/s12885-022-10239-6High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltrationSehui Kim0Jaemoon Koh1Seung Geun Song2Jeemin Yim3Miso Kim4Bhumsuk Keam5Young Tae Kim6Jihun Kim7Doo Hyun Chung8Yoon Kyung Jeon9Department of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Internal Medicine, Seoul National University College of MedicineDepartment of Internal Medicine, Seoul National University College of MedicineDepartment of Thoracic Surgery, Seoul National University Hospital, Seoul National University College of MedicineDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineAbstract 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.https://doi.org/10.1186/s12885-022-10239-6Hexokinase-2GlycolysisTumor microenvironmentTumor-infiltrating lymphocytesCD8 + T-cell to Treg ratioImmunotherapy |
| spellingShingle | Sehui Kim Jaemoon Koh Seung Geun Song Jeemin Yim Miso Kim Bhumsuk Keam Young Tae Kim Jihun Kim Doo Hyun Chung Yoon Kyung Jeon High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration BMC Cancer Hexokinase-2 Glycolysis Tumor microenvironment Tumor-infiltrating lymphocytes CD8 + T-cell to Treg ratio Immunotherapy |
| title | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration |
| title_full | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration |
| title_fullStr | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration |
| title_full_unstemmed | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration |
| title_short | High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration |
| title_sort | high tumor hexokinase 2 expression promotes a pro tumorigenic immune microenvironment by modulating cd8 regulatory t cell infiltration |
| topic | Hexokinase-2 Glycolysis Tumor microenvironment Tumor-infiltrating lymphocytes CD8 + T-cell to Treg ratio Immunotherapy |
| url | https://doi.org/10.1186/s12885-022-10239-6 |
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