Explant Modeling of the Immune Environment of Head and Neck Cancer

Shay Sharon, Thomas Duhen, Shelly Bambina, Jason Baird, Rom Leidner, Bryan Bell, Nardy Casap, Marka Crittenden, Swetha Vasudevan, Maria Jubran, Nataly Kravchenko-Balasha, Michael Gough*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Patients exhibit distinct responses to immunotherapies that are thought to be linked to their tumor immune environment. However, wide variations in outcomes are also observed in patients with matched baseline tumor environments, indicating that the biological response to treatment is not currently predictable using a snapshot analysis. To investigate the relationship between the immune environment of tumors and the biological response to immunotherapies, we characterized four murine head and neck squamous cell carcinoma (HNSCC) models on two genetic backgrounds. Using tumor explants from those models, we identified correlations between the composition of infiltrating immune cells and baseline cytokine profiles prior to treatment. Following treatment with PD-1 blockade, CTLA-4 blockade, or OX40 stimulation, we observed inter-individual variability in the response to therapy between genetically identical animals bearing the same tumor. These distinct biological responses to treatment were not linked to the initial tumor immune environment, meaning that outcome would not be predictable from a baseline analysis of the tumor infiltrates. We similarly performed the explant assay on patient HNSCC tumors and found significant variability between the baseline environment of the tumors and their response to therapy. We propose that tumor explants provide a rapid biological assay to assess response to candidate immunotherapies that may allow matching therapies to individual patient tumors. Further development of explant approaches may allow screening and monitoring of treatment responses in HNSCC.

Original languageAmerican English
Article number611365
JournalFrontiers in Oncology
Volume11
DOIs
StatePublished - 17 Jun 2021

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Sharon, Duhen, Bambina, Baird, Leidner, Bell, Casap, Crittenden, Vasudevan, Jubran, Kravchenko-Balasha and Gough.

Keywords

  • CTLA4
  • OX40
  • PD1
  • cytokine
  • explant
  • head and neck cancer
  • immunotherapy
  • tumor

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