Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. In this study, we define the role of homeobox protein B6 (HOXB6) and HOXB8 in controlling pancreatic cancer tumorigenesis and immune response. Transcriptomic an...
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| Format: | Article |
| Language: | English |
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Springer
2025-07-01
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| Series: | Molecular Biomedicine |
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| Online Access: | https://doi.org/10.1186/s43556-025-00292-5 |
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| author | Ludivine Bertonnier-Brouty Sara Bsharat Kavya Achanta Jonas Andersson Thanya Pranomphon Tania Singh Tuomas Kaprio Jaana Hagström Caj Haglund Hanna Seppänen Rashmi B. Prasad Isabella Artner |
| author_facet | Ludivine Bertonnier-Brouty Sara Bsharat Kavya Achanta Jonas Andersson Thanya Pranomphon Tania Singh Tuomas Kaprio Jaana Hagström Caj Haglund Hanna Seppänen Rashmi B. Prasad Isabella Artner |
| author_sort | Ludivine Bertonnier-Brouty |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. In this study, we define the role of homeobox protein B6 (HOXB6) and HOXB8 in controlling pancreatic cancer tumorigenesis and immune response. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting a re-initiation of developmental programs in pancreatic cancer. Specifically, we identified the transcription factors HOXB6 and HOXB8 as potential regulators in PDAC. We described their functions in pancreatic cancer by performing transcriptomic and tumor tissue microarray analyses, in vitro assays in pancreatic and lung cancer cell lines and co-culture experiments with immune cells. Loss of HOXB6 and HOXB8 in pancreatic cancer cells inhibited cell proliferation, induced apoptosis and senescence and enhanced gemcitabine sensitivity. Moreover, reduced HOXB6 and HOXB8 expression in pancreatic and lung adenocarcinoma cell lines affected transcription of immune response pathways which resulted in an increased sensitivity of cancer cells to anti-tumorigenic activities of macrophages suggesting that the HOXB6 and HOXB8 immune regulatory function is conserved in different cancer types. Additionally, naïve M0 macrophages exposed to HOXB8 deficient PDAC cells were unable to differentiate into tumor-associated macrophages, suggesting that HOXB8 promotes the transition of initial anti-tumor macrophage to a tumor-promoting macrophage phenotype in pancreatic cancer. Our findings indicate that HOXB6 and HOXB8 play important roles in regulating cell proliferation, immune response, and treatment resistance to promote pancreatic cancer tumorigenesis and could be useful therapeutic targets. |
| format | Article |
| id | doaj-art-988618689fa74bc8b6e687ffae8f2e73 |
| institution | Kabale University |
| issn | 2662-8651 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Molecular Biomedicine |
| spelling | doaj-art-988618689fa74bc8b6e687ffae8f2e732025-08-20T03:42:39ZengSpringerMolecular Biomedicine2662-86512025-07-016111810.1186/s43556-025-00292-5Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancerLudivine Bertonnier-Brouty0Sara Bsharat1Kavya Achanta2Jonas Andersson3Thanya Pranomphon4Tania Singh5Tuomas Kaprio6Jaana Hagström7Caj Haglund8Hanna Seppänen9Rashmi B. Prasad10Isabella Artner11Lund Stem Cell Center, Lund UniversityLund Stem Cell Center, Lund UniversityLund Stem Cell Center, Lund UniversityLund University Diabetes Center, Lund UniversityLund Stem Cell Center, Lund UniversityLund Stem Cell Center, Lund UniversityDepartment of Surgery, Helsinki University HospitalDepartment of Surgery, Helsinki University HospitalDepartment of Surgery, Helsinki University HospitalDepartment of Surgery, Helsinki University HospitalLund University Diabetes Center, Lund UniversityLund Stem Cell Center, Lund UniversityAbstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. In this study, we define the role of homeobox protein B6 (HOXB6) and HOXB8 in controlling pancreatic cancer tumorigenesis and immune response. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting a re-initiation of developmental programs in pancreatic cancer. Specifically, we identified the transcription factors HOXB6 and HOXB8 as potential regulators in PDAC. We described their functions in pancreatic cancer by performing transcriptomic and tumor tissue microarray analyses, in vitro assays in pancreatic and lung cancer cell lines and co-culture experiments with immune cells. Loss of HOXB6 and HOXB8 in pancreatic cancer cells inhibited cell proliferation, induced apoptosis and senescence and enhanced gemcitabine sensitivity. Moreover, reduced HOXB6 and HOXB8 expression in pancreatic and lung adenocarcinoma cell lines affected transcription of immune response pathways which resulted in an increased sensitivity of cancer cells to anti-tumorigenic activities of macrophages suggesting that the HOXB6 and HOXB8 immune regulatory function is conserved in different cancer types. Additionally, naïve M0 macrophages exposed to HOXB8 deficient PDAC cells were unable to differentiate into tumor-associated macrophages, suggesting that HOXB8 promotes the transition of initial anti-tumor macrophage to a tumor-promoting macrophage phenotype in pancreatic cancer. Our findings indicate that HOXB6 and HOXB8 play important roles in regulating cell proliferation, immune response, and treatment resistance to promote pancreatic cancer tumorigenesis and could be useful therapeutic targets.https://doi.org/10.1186/s43556-025-00292-5Homeobox protein B6 (HOXB6)Homeobox protein B8 (HOXB8)Fetal pancreasPancreatic cancerPancreatic ductal adenocarcinomaTumor-associated-macrophages |
| spellingShingle | Ludivine Bertonnier-Brouty Sara Bsharat Kavya Achanta Jonas Andersson Thanya Pranomphon Tania Singh Tuomas Kaprio Jaana Hagström Caj Haglund Hanna Seppänen Rashmi B. Prasad Isabella Artner Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer Molecular Biomedicine Homeobox protein B6 (HOXB6) Homeobox protein B8 (HOXB8) Fetal pancreas Pancreatic cancer Pancreatic ductal adenocarcinoma Tumor-associated-macrophages |
| title | Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer |
| title_full | Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer |
| title_fullStr | Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer |
| title_full_unstemmed | Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer |
| title_short | Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer |
| title_sort | homeobox protein b6 and homeobox protein b8 control immune cancer cell interactions in pancreatic cancer |
| topic | Homeobox protein B6 (HOXB6) Homeobox protein B8 (HOXB8) Fetal pancreas Pancreatic cancer Pancreatic ductal adenocarcinoma Tumor-associated-macrophages |
| url | https://doi.org/10.1186/s43556-025-00292-5 |
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