ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer
Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC....
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2190671 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850238189729480704 |
|---|---|
| author | Hae-Yun Jung Dae-Keum Lee Minwook Lee Seung Hee Choi Joo Dong Park Eun-Su Ko Jongwon Lee Kyung-Soon Park Hae-Yun Jung |
| author_facet | Hae-Yun Jung Dae-Keum Lee Minwook Lee Seung Hee Choi Joo Dong Park Eun-Su Ko Jongwon Lee Kyung-Soon Park Hae-Yun Jung |
| author_sort | Hae-Yun Jung |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Here, we show that targeting an ETS transcription factor ELK3 (ELK3) recruits immune cells including natural killer (NK) cells into tumors via the chemotactic activity of chemokine. ELK3 depletion increases CXCL16 expression level and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment in TNBC. In silico analysis showed that ELK3 is negatively correlated with CXCL16 expression in breast cancer patient samples. Low expression of ELK3 and high expression of CXCL16 were associated with a better prognosis. Low expression of ELK3 and high expression of CXCL16 were associated with increased expression of NK cell-related genes. Our findings demonstrate that the ELK3-CXCL16 axis modulates NK cell recruitment to increase NK cell cytotoxicity, suggesting that targeting the ELK3 gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC. |
| format | Article |
| id | doaj-art-1cedfa1b2b9d4585a21472ff92ee5c92 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-1cedfa1b2b9d4585a21472ff92ee5c922025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2190671ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancerHae-Yun Jung0Dae-Keum Lee1Minwook Lee2Seung Hee Choi3Joo Dong Park4Eun-Su Ko5Jongwon Lee6Kyung-Soon Park7Hae-Yun Jung8Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaBrain Korea 21 Plus Project for Biomedical Science, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of KoreaTriple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Here, we show that targeting an ETS transcription factor ELK3 (ELK3) recruits immune cells including natural killer (NK) cells into tumors via the chemotactic activity of chemokine. ELK3 depletion increases CXCL16 expression level and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment in TNBC. In silico analysis showed that ELK3 is negatively correlated with CXCL16 expression in breast cancer patient samples. Low expression of ELK3 and high expression of CXCL16 were associated with a better prognosis. Low expression of ELK3 and high expression of CXCL16 were associated with increased expression of NK cell-related genes. Our findings demonstrate that the ELK3-CXCL16 axis modulates NK cell recruitment to increase NK cell cytotoxicity, suggesting that targeting the ELK3 gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2190671CXCL16ELK3immunosuppressive tumor microenvironmentNK cell cytotoxicityNK cell recruitmenttriple-negative breast cancer |
| spellingShingle | Hae-Yun Jung Dae-Keum Lee Minwook Lee Seung Hee Choi Joo Dong Park Eun-Su Ko Jongwon Lee Kyung-Soon Park Hae-Yun Jung ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer OncoImmunology CXCL16 ELK3 immunosuppressive tumor microenvironment NK cell cytotoxicity NK cell recruitment triple-negative breast cancer |
| title | ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer |
| title_full | ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer |
| title_fullStr | ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer |
| title_full_unstemmed | ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer |
| title_short | ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer |
| title_sort | elk3 cxcl16 axis determines natural killer cell cytotoxicity via the chemotactic activity of cxcl16 in triple negative breast cancer |
| topic | CXCL16 ELK3 immunosuppressive tumor microenvironment NK cell cytotoxicity NK cell recruitment triple-negative breast cancer |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2190671 |
| work_keys_str_mv | AT haeyunjung elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT daekeumlee elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT minwooklee elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT seungheechoi elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT joodongpark elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT eunsuko elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT jongwonlee elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT kyungsoonpark elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer AT haeyunjung elk3cxcl16axisdeterminesnaturalkillercellcytotoxicityviathechemotacticactivityofcxcl16intriplenegativebreastcancer |