ANO6-mediated trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer cell growth and immune suppression

@article{ogier2026ano6mediated,
  title = {{ANO6-mediated trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer cell growth and immune suppression}},
  author = {Charline Ogier and Charles Solomon Akino Mercy and Elena Bondarenko and Zhijing Wu and Zhen Lu and Quoc Thang Bui and Mayura R. Dhamdhere and Yingying Tang and Ludmila Recoules and Alena Klochkova and Linara Gabitova-Cornell and Battuya Bayarmagnai and Diana Restifo and Aizhan Surumbayeva and Debora Barbosa Vendramini Costa and Alexander Y. Deneka and Ralph Francescone and Anna C. Lilly and Alyssa Sipman and Jaye C. Gardiner and Tiffany Luong and Janusz Franco‐Barraza and Alexander A. Dolskiy and Mariia Dmitrieva and Kathy Qi Cai and Margret B. Einarson and Emmanuelle Nicolas and Andrei Efimov and Emily Megill and Nathaniel W. Snyder and Sven Miller and Mark Andrake and Natalie Phinney and Rolf A. Brekken and Jerome F. Cros and Erica A. Golemis and Yunyun Zhou and Bojana Gligorijevic and Corinne Bousquet and Jonathan Soboloff and Serge Yu. Fuchs and Edna Cukierman and Igor A. Astsaturov},
  journal = {Nature Cancer},
  year = {2026},
  month = oct,
  doi = {10.1038/s43018-026-01265-5},
  url = {https://doi.org/10.1038/s43018-026-01265-5},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - ANO6-mediated trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer cell growth and immune suppression
AU  - Charline Ogier
AU  - Charles Solomon Akino Mercy
AU  - Elena Bondarenko
AU  - Zhijing Wu
AU  - Zhen Lu
AU  - Quoc Thang Bui
AU  - Mayura R. Dhamdhere
AU  - Yingying Tang
AU  - Ludmila Recoules
AU  - Alena Klochkova
AU  - Linara Gabitova-Cornell
AU  - Battuya Bayarmagnai
AU  - Diana Restifo
AU  - Aizhan Surumbayeva
AU  - Debora Barbosa Vendramini Costa
AU  - Alexander Y. Deneka
AU  - Ralph Francescone
AU  - Anna C. Lilly
AU  - Alyssa Sipman
AU  - Jaye C. Gardiner
AU  - Tiffany Luong
AU  - Janusz Franco‐Barraza
AU  - Alexander A. Dolskiy
AU  - Mariia Dmitrieva
AU  - Kathy Qi Cai
AU  - Margret B. Einarson
AU  - Emmanuelle Nicolas
AU  - Andrei Efimov
AU  - Emily Megill
AU  - Nathaniel W. Snyder
AU  - Sven Miller
AU  - Mark Andrake
AU  - Natalie Phinney
AU  - Rolf A. Brekken
AU  - Jerome F. Cros
AU  - Erica A. Golemis
AU  - Yunyun Zhou
AU  - Bojana Gligorijevic
AU  - Corinne Bousquet
AU  - Jonathan Soboloff
AU  - Serge Yu. Fuchs
AU  - Edna Cukierman
AU  - Igor A. Astsaturov
PY  - 2026
DA  - 2026/10/30
JO  - Nature Cancer
DO  - 10.1038/s43018-026-01265-5
UR  - https://doi.org/10.1038/s43018-026-01265-5
AB  - In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of the tumor mass and is remarkably devoid of functional blood vessels. This raises an unresolved question of how PDAC cells obtain essential metabolites and water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in obtaining and transferring lipids from blood-borne particles to PDAC cells via trogocytosis of CAF plasma membranes. We have also determined that CAF-expressed phospholipid scramblase anoctamin 6 (ANO6) is an essential CAF trogocytosis regulator required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membranes contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membrane initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells. Importantly, ANO6-dependent trogocytosis also supports the immunosuppressive function of pancreatic CAFs towards cytotoxic T cells by promoting transfer of excessive amounts of cholesterol. Further, blockade of ANO6 antagonizes tumor growth via disruption of delivery of exogenous cholesterol to cancer cells and reverses immune suppression suggesting a potential new strategy for PDAC therapy.
SN  - 2662-1347
ER  -