Introduction The immunogenic tumor microenvironment (TME) is a main focus of cancer research.
Many different immunosuppressive mechanisms have been identified. Over the last years
it has become evident that the adenosine signalling pathway and its suppressive function
on effector cells of the immune system influence tumor growth and therapeutic success.
Materials & Methods The cellular immune system of an immunocompetent HNSCC mouse model (C3H/HeN) was
analysed by flow cytometry and immunohistochemistry. Inhibition of the adenosine signalling
pathway was achieved by systemic blocking of the adenosine receptor A2A (ADORA2A).
Results Tumor formation leads to a complex immune response in immunocompetent mice. Beside
significant alterations in the immunogenic microenvironment of the tumor, the immune
cell populations obtained from blood, spleen and bone marrow showed significant changes
over time. In mice, inhibition of ADORA2A on lymphocytes leads to a significant reduction
in tumor mass and to an increased migration of regulatory T-cells and mature B-cells
into the tumor tissue. In addition, germinal center-like-structures within the tumor
tissue have been detected.
Conclusion We characterized a powerful tool to investigate the influence of different immune
cell populations on tumor growth as well as for the investigation of new immunomodulatory
cancer therapies. We showed a complex immunogenic reaction in different organs during
tumor growth. By blocking the adenosine signaling pathway on lymphocytes, a drastic
change in the immunogenic microenvironment of the tumor promotes antitumor function
in HNSCC bearing C3H/HeN mice. Therefore, the adenosine signaling pathway represent
a promising target for new therapeutic strategies for HNSCC treatment.
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