Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer.

Journal for Immunotherapy of Cancer
Kenji FujiwaraLei Zheng

Abstract

Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia of PDACs following neoadjuvant therapy including RT, suggesting RT may prime PDAC for PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i) treatments. In this study, we investigated the antitumor efficacy of the combination therapies with radiation and PD-1 blockade or IDO1 inhibition or both. We developed and used a mouse syngeneic orthotopic model of PDAC suitable for hypofractionated RT experiments. The combination therapy of αPD-1 and RT improved survival. The dual combination of RT/IDO1i and triple combination of RT/αPD-1/IDO1i did not improve survival compared with RT/αPD-1, although all of these combinations offer similar local tumor control. RT/αPD-1 appeared to result in the best systemic interferon-γ response compared with other treatment groups and the highest local expression of immune-activation genes, including Cd28 and Icos. Our RT model allows ex...Continue Reading

References

Sep 17, 2002·Cell Death and Differentiation·F FallarinoP Puccetti
Oct 4, 2005·International Journal of Radiation Oncology, Biology, Physics·Sandra DemariaSilvia C Formenti
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesca FallarinoPaolo Puccetti
Jul 4, 2009·The Lancet Oncology·Silvia C Formenti, Sandra Demaria
Jun 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie R BrahmerSuzanne L Topalian
Sep 15, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jean-Luc Van LaethemKarin Haustermans
Mar 9, 2012·The New England Journal of Medicine·Michael A PostowJedd D Wolchok
Jan 19, 2013·Journal of Visualized Experiments : JoVE·Elaine BigelowLei Zheng
Mar 12, 2013·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·Jin HeChristopher L Wolfgang
Apr 9, 2013·International Journal of Radiation Oncology, Biology, Physics·Michael D ChuongRavi Shridhar
May 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hua LiangYang-Xin Fu
Jan 3, 2014·The Journal of Clinical Investigation·Liufu DengYang-Xin Fu
Jul 30, 2014·Oncoimmunology·Encouse B GoldenSilvia C Formenti
Dec 24, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Naoyuki NogamiKatsuyuki Kiura
Jun 26, 2015·Human Vaccines & Immunotherapeutics·Adrian G Murphy, Lei Zheng
Aug 5, 2015·International Journal of Radiation Oncology, Biology, Physics·Daniel L J ThorekJames Russell
Sep 1, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M DucreuxUNKNOWN ESMO Guidelines Committee
Mar 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arta M MonjazebWilliam J Murphy
Apr 21, 2016·Journal of Biomolecular Screening·Huaping TangMary Ellen Cvijic
Sep 16, 2016·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·S AllampatiS L Gabbard
Dec 10, 2016·EMBO Molecular Medicine·Abul AzadEmmanouil Fokas
Oct 27, 2017·Cancer Immunology Research·Ingunn M StromnesSunil R Hingorani
Dec 2, 2017·The Surgical Clinics of North America·Evan Landau, Shalom Kalnicki
Dec 19, 2017·The Breast : Official Journal of the European Society of Mastology·Jason C Ye, Silvia C Formenti
Feb 10, 2018·Immunotherapy·Maureen L AliruSunil Krishnan
Mar 4, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Erik LadomerskyDerek A Wainwright
Mar 15, 2018·International Journal of Radiation Oncology, Biology, Physics·Xuanwei Zhang, Gabriele Niedermann
Sep 29, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tara C MitchellThomas F Gajewski
Oct 31, 2018·Seminars in Immunopathology·Emmett V Schmidt
Nov 9, 2018·International Journal of Molecular Sciences·Shravanti MacherlaMahvish Muzaffar
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jan 20, 2019·Current Oncology Reports·Mayanne M T ZhuTorsten O Nielsen
Feb 13, 2019·The Journal of Clinical Investigation·Alex B BlairLei Zheng

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection
flow cytometry

Software Mentioned

NanoString
Base package
dplyr
reshape2
GraphPad
Plex
CRAN
NanoString nSolver
multtest
tidyr

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.