Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function
DC Field | Value | Language |
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dc.contributor.author | Kim, Hye Ryun | - |
dc.contributor.author | Park, Hyo Jin | - |
dc.contributor.author | Son, Jimin | - |
dc.contributor.author | Lee, Jin Gu | - |
dc.contributor.author | Chung, Kyung Young | - |
dc.contributor.author | Cho, Nam Hoon | - |
dc.contributor.author | Shim, Hyo Sup | - |
dc.contributor.author | Park, Seyeon | - |
dc.contributor.author | Kim, Gamin | - |
dc.contributor.author | Yoon, Hong In | - |
dc.contributor.author | Kim, Hyun Gyung | - |
dc.contributor.author | Jung, Yong Woo | - |
dc.contributor.author | Cho, Byoung Chul | - |
dc.contributor.author | Park, Seong Yong | - |
dc.contributor.author | Rha, Sun Young | - |
dc.contributor.author | Ha, Sang-Jun | - |
dc.date.accessioned | 2021-08-31T21:25:56Z | - |
dc.date.available | 2021-08-31T21:25:56Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2019-12-04 | - |
dc.identifier.issn | 2051-1426 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/60956 | - |
dc.description.abstract | Background: Regulatory T (Treg) cells have an immunosuppressive function in cancer, but the underlying mechanism of immunosuppression in the tumor microenvironment (TME) is unclear. Methods: We compared the phenotypes of T cell subsets, including T-reg cells, obtained from peripheral blood, malignant effusion, and tumors of 103 cancer patients. Our primary focus was on the expression of immune checkpoint (IC)-molecules, such as programmed death (PD)-1, T-cell immunoglobulin and mucin-domain containing (TIM)-3, T cell Ig and ITIM domain (TIGIT), and cytotoxic T lymphocyte antigen (CTLA)-4, on T-reg cells in paired lymphocytes from blood, peritumoral tissue, and tumors of 12 patients with lung cancer. To identify the immunosuppressive mechanisms acting on tumor-infiltrating Treg cells, we conducted immunosuppressive functional assays in a mouse model. Results: CD8(+), CD4(+) T cells, and T-reg cells exhibited a gradual upregulation of IC-molecules the closer they were to the tumor. Interestingly, PD-1 expression was more prominent in T-reg cells than in conventional T (T-conv) cells. In lung cancer patients, higher levels of IC-molecules were expressed on T-reg cells than on T-conv cells, and T-reg cells were also more enriched in the tumor than in the peri-tumor and blood. In a mouse lung cancer model, IC-molecules were also preferentially upregulated on T-reg cells, compared to T-conv cells. PD-1 showed the greatest increase on most cell types, especially T-reg cells, and this increase occurred gradually over time after the cells entered the TME. PD-1 high-expressing tumor-infiltrating T-reg cells displayed potent suppressive activity, which could be partially inhibited with a blocking anti-PD-1 antibody. Conclusions: We demonstrate that the TME confers a suppressive function on T-reg cells by upregulating IC-molecule expression. Targeting IC-molecules, including PD-1, on T-reg cells may be effective for cancer treatment. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.subject | PROGRAMMED DEATH 1 | - |
dc.subject | NK CELLS | - |
dc.subject | PD-1 | - |
dc.subject | EXPRESSION | - |
dc.subject | SURVIVAL | - |
dc.subject | ANTIBODY | - |
dc.subject | CTLA-4 | - |
dc.subject | LYMPHOCYTES | - |
dc.subject | PD-1/PD-L1 | - |
dc.subject | RESPONSES | - |
dc.title | Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jung, Yong Woo | - |
dc.identifier.doi | 10.1186/s40425-019-0785-8 | - |
dc.identifier.scopusid | 2-s2.0-85076033947 | - |
dc.identifier.wosid | 000511123200002 | - |
dc.identifier.bibliographicCitation | JOURNAL FOR IMMUNOTHERAPY OF CANCER, v.7, no.1 | - |
dc.relation.isPartOf | JOURNAL FOR IMMUNOTHERAPY OF CANCER | - |
dc.citation.title | JOURNAL FOR IMMUNOTHERAPY OF CANCER | - |
dc.citation.volume | 7 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | PROGRAMMED DEATH 1 | - |
dc.subject.keywordPlus | NK CELLS | - |
dc.subject.keywordPlus | PD-1 | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | ANTIBODY | - |
dc.subject.keywordPlus | CTLA-4 | - |
dc.subject.keywordPlus | LYMPHOCYTES | - |
dc.subject.keywordPlus | PD-1/PD-L1 | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordAuthor | Tumor microenvironment | - |
dc.subject.keywordAuthor | Regulatory T cells | - |
dc.subject.keywordAuthor | Immune checkpoints | - |
dc.subject.keywordAuthor | Programmed cell death 1 receptor | - |
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