Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer

Bertonnier-Brouty, Ludivine LU ; Bsharat, Sara LU ; Achanta, Kavya LU ; Andersson, Jonas LU ; Pranomphon, Thanya LU ; Singh, Tania LU ; Kaprio, Tuomas ; Hagström, Jaana ; Haglund, Caj and Seppänen, Hanna , et al. (2025) In Molecular biomedicine 6(1).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Homeodomain Proteins/genetics, Pancreatic Neoplasms/immunology, Cell Line, Tumor, Carcinoma, Pancreatic Ductal/genetics, Cell Proliferation, Gene Expression Regulation, Neoplastic, Macrophages/metabolism, Cell Communication/immunology, Apoptosis/genetics, Deoxycytidine/analogs & derivatives, Gemcitabine
in
Molecular biomedicine
volume
6
issue
1
article number
48
publisher
Springer International Publishing
external identifiers
  • scopus:105010131272
  • pmid:40619489
ISSN
2662-8651
DOI
10.1186/s43556-025-00292-5
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
cd1045a7-eb54-4ac9-a219-a1d57956d532
date added to LUP
2025-07-18 17:02:53
date last changed
2025-07-21 12:36:30
@article{cd1045a7-eb54-4ac9-a219-a1d57956d532,
  abstract     = {{<p>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.</p>}},
  author       = {{Bertonnier-Brouty, Ludivine and Bsharat, Sara and Achanta, Kavya and Andersson, Jonas and Pranomphon, Thanya and Singh, Tania and Kaprio, Tuomas and Hagström, Jaana and Haglund, Caj and Seppänen, Hanna and Prasad, Rashmi B and Artner, Isabella}},
  issn         = {{2662-8651}},
  keywords     = {{Humans; Homeodomain Proteins/genetics; Pancreatic Neoplasms/immunology; Cell Line, Tumor; Carcinoma, Pancreatic Ductal/genetics; Cell Proliferation; Gene Expression Regulation, Neoplastic; Macrophages/metabolism; Cell Communication/immunology; Apoptosis/genetics; Deoxycytidine/analogs & derivatives; Gemcitabine}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  publisher    = {{Springer International Publishing}},
  series       = {{Molecular biomedicine}},
  title        = {{Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1186/s43556-025-00292-5}},
  doi          = {{10.1186/s43556-025-00292-5}},
  volume       = {{6}},
  year         = {{2025}},
}