Introduction:
Advanced HNCs often evade standard therapies. The lack of alternative treatment options
limit patient prognosis. Here, we investigated the effect of alternative immunotherapies
in a tumor mouse model.
Methods:
6-week C57BL/6 WT mice received 4-Nitroquinoline-1-oxide (4-NQO) containing drinking
water for 16 weeks. At week (w) 16 mice were randomly assigned to different study
groups: 1. Monotherapies: Polyepitope (BRAF, EGFR, EphA2, EphA2, p53, PDGFR, STAT3,
Survivin and VEGFR2) vaccination (VAC), Cisplatin (CIS), Low/High dose Adenosine Receptor
Antagonist A2AR (lAR/hAR), 2. Combinations: VAC+CIS, VAC+ hAR. The body weight of
the mice was assessed throughout the course of the experiment. CD8+ T-cell dependent
vaccination responses and levels of MDSC (CD11b+Gr1+) and Treg (CD4+Foxp3+) were monitored
at w21/25. Tongue and esophagus tumor volumes were compared at the end of the experiment.
Results:
Monotherapy with vaccine showed only transient improvement in body weight, MDSC and
Treg levels and no difference in tumor sizes compared to the control group. CIS monotherapy
demonstrated less body weight and also reduced tumor volume. However, hAR (and less
lAR) led to increased average weight, reduced tumor volume and low Treg levels. Combinational
treatment with VAC+CIS and VAC+hAR didn't improve body weight, tumor volume and showed
no effect on regulatory cells.
Conclusions:
Our results emphasize that monotherapy with hAR is quite promising. However, for combinational
treatment the data underline the need for further investigations to refine immunotherapies
in the future.
