Analysis of suppressive B cell populations and their role in cancer induced immune response in head and neck squamous cell carcinoma (HNSCC) in mouse and humans

Introduction:

The immunogenic tumor microenvironment is a main focus of cancer research. Many different immunosuppressive mechanisms have been identified. Over the last years it became evident that, besides T cells, tumor infiltrating regulatory B cells (Breg) influence tumor growth and affect therapeutic success.

Methods:

The inhibition of the ADO pathway by blocking the adenosine A2A receptor (ADORA2A) was analysed in an immunocompetent murine HNSCC model. The populations of tumor infiltrating lymphocytes were analysed by flow cytometry and immunohistochemistry and compared with human HNSCC blood and tumor samples.

Results:

In humans and mice, a high proportion of blood and tumor B cells express CD39 and CD73, which mediate ADO production. In mice, inhibition of ADORA2A, mainly expressed on lymphocytes, significantly reduced tumor mass, increased tumor B cell infiltration and changes the immunogenic tumor microenvironment. Additionally to immune-suppressive Breg we observed B cells organized in germinal center-like-structures within tumor tissue, suggesting B cell mediated activity against tumor growth.

Conclusion:

We created a powerful tool to investigate the impact of certain B cell populations on tumor growth as well as for the development of novel immune-modulatory cancer treatments. For the first time, we unveiled the presence of a CD39+CD73+ Breg population within the tumor-microenvironment in HNSCC-bearing mice and therefore a situation that is comparable to human HNSCC. Furthermore, we revealed a drastic change in the immunogenic microenvironment of the tumor by blocking the ADO pathway on lymphocytes in HNSCC bearing mice. Therefore, a more precise investigation of the ADO pathway could help to develop new therapeutic strategies for HNSCC treatment.

Publication History

Publication Date:
23 April 2019 (online)