Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases

Science
Arnaud PommierDouglas T Fearon

Abstract

The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intraportal injection of immunogenic PDA cells into preimmunized mice seeded livers only with single, nonreplicating DCCs that were CK19- and MHCI- The DCCs exhibited an endoplasmic reticulum (ER) stress response but paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s). Inducible expression of XBP1s in DCCs, in combination with T cell depletion, stimulated the outgrowth of macrometastatic lesions that expressed CK19 and MHCI. Thus, unresolved ER stress enables DCCs to escape immunity and establish latent metastases.

References

Sep 1, 1993·Journal of the National Cancer Institute·K PantelG Riethmüller
Sep 19, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Anirban MaitraRalph H Hruban
May 31, 1965·JAMA : the Journal of the American Medical Association·D C MARTINV J ROSEN
Jul 11, 2006·Science·Julie Hollien, Jonathan S Weissman
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sérgio F de AlmeidaMaria de Sousa
Nov 21, 2007·Nature·Catherine M KoebelRobert D Schreiber
Aug 13, 2008·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·D HariharanH M Kocher
Jan 10, 2009·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·A Van den BroeckB Topal
Feb 18, 2009·BMC Immunology·Diana P GranadosClaude Perreault
Dec 30, 2009·Deutsches Ärzteblatt International·Volker KeimMichael H Schoenberg
May 11, 2010·The Lancet Oncology·Dirk C Strauss, J Meirion Thomas
May 27, 2010·The Journal of Clinical Investigation·Jo EylesJean-Pierre Abastado
Nov 13, 2012·Advances in Experimental Medicine and Biology·Maria Soledad SosaJulio A Aguirre-Ghiso
Nov 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christine FeigDouglas T Fearon
May 16, 2014·Cancer Cell·Hanna J ClarkeStefan J Marciniak
Aug 15, 2014·Nature Reviews. Cancer·María Soledad SosaJulio A Aguirre-Ghiso
Sep 18, 2014·Journal of Experimental & Clinical Cancer Research : CR·Liang FangLihua Chen
Jan 6, 2015·Cell·Sylvia F BojDavid A Tuveson
Jun 9, 2015·Clinical Nuclear Medicine·Richard KimAmit Mahipal
Jan 23, 2016·Nature·Joan Massagué, Anna C Obenauf
Jan 23, 2016·Current Opinion in Immunology·Federico GarridoThorbald van Hall
Mar 5, 2016·Gastroenterology Research and Practice·Qiubo ZhangKaihong Huang
Mar 26, 2016·Cell·Srinivas MalladiJoan Massagué
Sep 16, 2016·Nature Communications·Nicole M AielloBen Z Stanger
Nov 3, 2016·Nature Reviews. Clinical Oncology·Malte MohmeKlaus Pantel
Nov 10, 2016·Cell Metabolism·Thomas R FlintDouglas T Fearon
Dec 23, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David BalliRobert H Vonderheide
Jul 7, 2017·Nature·Nicole M AielloBen Z Stanger
Jul 19, 2017·Trends in Cancer·Hélène VanackerMarie-Cécile Michallet
Oct 27, 2017·Cancer Immunology Research·Ingunn M StromnesSunil R Hingorani

❮ Previous
Next ❯

Citations

Jul 10, 2018·Nature Reviews. Gastroenterology & Hepatology·Clemens Thoma
Sep 29, 2018·Science·Julio A Aguirre-Ghiso
Aug 29, 2019·Nature Reviews. Cancer·Johannes G ReiterBert Vogelstein
May 19, 2019·Clinical & Experimental Metastasis·Andries ZijlstraUNKNOWN Board Members of the Metastasis Research Society
Jul 30, 2019·Frontiers in Oncology·Maria Laura De AngelisAnn Zeuner
May 8, 2020·Nature·Keisuke YamamotoAlec C Kimmelman
Aug 28, 2020·Frontiers in Oncology·Longyong XuXi Chen
Aug 27, 2019·Frontiers in Immunology·Kangsan KimSrinivas Malladi
Jun 24, 2020·Journal of Hematology & Oncology·Minlin JiangCaicun Zhou
Oct 27, 2018·Nature Cell Biology·Erica T GoddardCyrus M Ghajar
Apr 24, 2020·Nature·Anirban Maitra
Jul 1, 2020·Chemical Society Reviews·A Paden King, Justin J Wilson
Mar 21, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Jun 4, 2020·Nature Reviews. Cancer·Tri Giang Phan, Peter I Croucher
Dec 22, 2019·Genes·Marina Ayres Pereira, Iok In Christine Chio
Feb 8, 2020·Cells·Francisco Triana-MartínezEduardo Domínguez
Oct 8, 2020·International Journal of Molecular Sciences·Dimitrios KorentzelosAlan Wells
Nov 16, 2020·The FEBS Journal·Maartje P F DamenColinda L G J Scheele
Dec 1, 2020·Frontiers in Oncology·Luigi Ombrato, Marco Montagner
Dec 20, 2019·Cancer Discovery·John Kwon, Samuel F Bakhoum
Jan 15, 2021·Nature Medicine·Karuna Ganesh, Joan Massagué
Nov 20, 2020·Cancers·Julien Schaller, Judith Agudo
Jan 16, 2021·Cancers·Claire M RobinsonAfshin Samali
Nov 21, 2020·Nature Reviews. Cancer·Xi Chen, Juan R Cubillos-Ruiz
Feb 15, 2021·Seminars in Cancer Biology·Alexandre CorthayColin C Anderson
Nov 17, 2020·Frontiers in Immunology·Antonella SistiguRuggero De Maria
Feb 5, 2021·Nature Communications·Paulino Tallón de LaraMaries van den Broek
May 8, 2019·Developmental Cell·FuiBoon KaiValerie M Weaver
Apr 17, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Mar 9, 2021·Nature Cancer·Emma RissonJulio A Aguirre-Ghiso
Mar 7, 2021·Cells·Michael R ShurinGalina V Shurin
Mar 20, 2021·Frontiers in Cell and Developmental Biology·Alberto Hernández-BarrancoHéctor Peinado
Mar 21, 2021·Nature Reviews. Gastroenterology & Hepatology·Joel Encarnación-Rosado, Alec C Kimmelman
Mar 26, 2020·Developmental Cell·Alba Roca Portoles, Stephen W G Tait
Mar 25, 2021·Nature Reviews. Cancer·Houjun XiaWeiping Zou
Mar 24, 2021·Immunity·Maria Tello-LafozEkrem Emrah Er

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Ductal

Ductal carcinoma is a malignant neoplasm involving the ductal systems of any of a number of organs, such as the mammary glands, pancreas, prostate or lacrimal gland. Discover the latest research on ductal carcinoma here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.