Evaluation of Explant Responses to STING Ligands: Personalized Immunosurgical Therapy for Head and Neck Squamous Cell Carcinoma

Cancer Research
Jason R BairdMichael J Gough

Abstract

Surgeons have unique in situ access to tumors enabling them to apply immunotherapies to resection margins as a means to prevent local recurrence. Here, we developed a surgical approach to deliver stimulator of interferon genes (STING) ligands to the site of a purposeful partial tumor resection using a gel-based biomaterial. In a range of head and neck squamous cell carcinoma (HNSCC) murine tumor models, we demonstrate that although control-treated tumors recur locally, tumors treated with STING-loaded biomaterials are cured. The mechanism of tumor control required activation of STING and induction of type I IFN in host cells, not cancer cells, and resulted in CD8 T-cell-mediated cure of residual cancer cells. In addition, we used a novel tumor explant assay to screen individual murine and human HNSCC tumor responses to therapies ex vivo We then utilized this information to personalize the biomaterial and immunotherapy applied to previously unresponsive tumors in mice. These data demonstrate that explant assays identify the diversity of tumor-specific responses to STING ligands and establish the utility of the explant assay to personalize immunotherapies according to the local response.Significance: Delivery of immunotherapy dir...Continue Reading

References

Apr 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael GoughRichard Vile
Jul 3, 2008·Cancer Research·Michael J GoughAndrew D Weinberg
Mar 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hailing LuMary L Disis
Dec 16, 2010·Journal of Pharmacological and Toxicological Methods·Devon D EgenolfPeter J Bugelski
Nov 17, 2011·Cancer Research·Nancy P JuddRavindra Uppaluri
Dec 29, 2012·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Matteo Alicandri-CiufelliPier Franco Conte
Apr 23, 2013·The EMBO Journal·Taner CavlarVeit Hornung
Apr 25, 2017·The Journal of Clinical Investigation·Tyrel T SmithMatthias T Stephan
Jul 21, 2017·JCI Insight·Zipei FengBernard A Fox
Sep 6, 2017·International Journal of Radiation Oncology, Biology, Physics·Jason R BairdMichael J Gough
Oct 4, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bas D KosterTanja D de Gruijl
Feb 18, 2018·Biomaterials·David G LeachJeffrey D Hartgerink
Mar 23, 2018·Science Translational Medicine·Chun Gwon ParkMichael S Goldberg

❮ Previous
Next ❯

Citations

Dec 25, 2019·The Journal of Clinical Investigation·Xiaobo LuoYu L Lei
Dec 4, 2019·Medicinal Research Reviews·Jun-Jun WuYan-Mei Li
Mar 25, 2020·MedChemComm·Herman O SintimMoloud A Sooreshjani
Sep 6, 2020·Molecular Cancer·Yang WangXiawei Wei
Nov 5, 2019·Molecular Cancer·Yuanyuan ZhuXiaobo Li
Jan 10, 2020·Annual Review of Pharmacology and Toxicology·Michaela Gebauer, Arne Skerra
Oct 22, 2020·Journal of Clinical Medicine·Leila Motedayen AvalDavid J Pinato
May 10, 2020·Seminars in Radiation Oncology·Leo Y LuoAmit Maity
Dec 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Huashan DuManhua Cui
Jan 21, 2021·ACS Biomaterials Science & Engineering·David G LeachSimon Young
Feb 17, 2019·Acta Biomaterialia·David G LeachJeffrey D Hartgerink
Jun 28, 2019·Biomaterials·Cameron LouttitJames J Moon
Mar 13, 2021·The Journal of Biological Chemistry·Kathleen M McAndrewsRaghu Kalluri
Apr 6, 2021·Frontiers in Oncology·Terry R MedlerMichael J Gough
Apr 11, 2021·Journal for Immunotherapy of Cancer·Brendan D CurtiWilliam L Redmond
Jul 6, 2021·Frontiers in Oncology·Shay SharonMichael Gough
Aug 10, 2020·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Vuk BortnikAdi Idris

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.