IADR Abstract Archives

Determination of Immune Evasion Phenotypes of HNSCC

Objectives: The programmed death (PD-1/PD-L1) pathway is the focus of immunotherapeutic checkpoint inhibition for the control of head and neck squamous cell carcinoma (HNSCC). However, it may be only part of the total immunosuppressive biomarker profile of these cells. The objective of this study was to determine immunosuppressive biomarker profiles to identify immune evasion phenotypes of HNSCC using a computational and experimental approach.

Methods: A computational simulation model was developed and used to predict immunosuppressive biomarker profiles and HNSCC (UM-SCC) cells grown in culture were used to confirm the responses. 1.0 × 106 viable cells/ml of SCC4, SCC15, SCC25, SCC19, SCC84, SCC92, and SCC99 were incubated in culture for 24 hours. RPMI-1640 was removed and concentrations of extracellular biomarkers were determined (Milliplex immunoassays, Millipore, Billerica, MA). Adherent cells were lysed and concentrations of cell associated biomarkers were determined (ELISA, American Research Products, Inc., Waltham, MA). An analogous two-way fixed effect ANOVA was fit to log-transformed concentrations of biomarkers (JMP10, SAS, Cary, NC) and pairwise group comparisons were conducted at the 0.05 level using the method of Tukey’s Honest Significant Differences (HSD).
Results: There was an average of 85% correlation between predictive vs. experimental biomarker trends for SCC4, SCC15, and SCC25 when comparing 2 cell lines at a time. In culture, SCC cell lines produced different concentrations of immunosuppressive biomarkers including IL6, IL10, TGFβ, VEGF, FASL, CD47, IDO, PD-L1 and other chemokines and cytokines. SCC4, SCC15, SCC25, and SCC99 cell lines produced significantly higher concentrations (p<0.05) of immunosuppressive biomarkers than SCC19, SCC84, and SCC92 cell lines.
Conclusions: Expression of immunosuppressive biomarkers by HNSCC cell lines can be determined based on their profile of genomic aberrations using a computational approach. These cells likely represent different immune evasion phenotypes, a finding that will clearly impact the type of immunotherapy used to treat patients with HNSCC.
AADR/CADR Annual Meeting
2016 AADR/CADR Annual Meeting (Los Angeles, California)
Los Angeles, California
2016
0962
  • Treinen Christopher  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Vali Shireen  ( CellWorks Group, Inc. , San Jose San Jose , Iowa , United States )
  • Brogden Kim  ( University of Iowa , Iowa City Iowa City , Iowa , United States ;  University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Gomez Hernandez Maria Paula  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Bates Amber  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Recker Erica  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Lanzel Emily  ( The University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Fischer Carol  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Johnson Georgia  ( University of Iowa , Iowa City Iowa City , Iowa , United States )
  • Guthmiller Janet  ( University of Nebraska Medical Center , Lincoln Lincoln , Nebraska , United States )
  • Abbasi Taher  ( CellWorks Group, Inc. , San Jose San Jose , Iowa , United States )
  • NIH R01 DE014390, NIH T90 DE023520
    Kim A. Brogden, Christopher N. Treinen, Maria Paula Gomez Hernandez, Amber M. Bates, Erica N. Recker, Emily A. Lanzel, Carol L. Fischer, Georgia K. Johnson, and Janet M. Guthmiller declare no competing financial interests in the findings of this study or
    Oral Session
    Microbiology/Immunology-Host Bacterial Interactions I
    Friday, 03/18/2016 , 10:45AM - 12:15PM