Monotherapy with a A2A Adenosine Receptor Antagonist Reduces Tumor Volume in a 4-NQO-induced Head and Neck Cancer (HNC) Mouse Model

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.

Publication History

Publication Date:
23 April 2019 (online)