Analyses of germinal center B cells and tertiary lymphoid structures (TLS) in mouse and human HNSCC

Introduction:

Over the last years it became evident that, besides T cells, tumor infiltrating B cells influence tumor growth in a way that they affect the therapeutic success. Especially the presence of recently detected tertiary lymphoid structures with germinal-center-like-structures was linked to protective immune responses but also to deleterious outcomes in patients.

Materials and methods:

We have established a mouse model for head and neck squamous cell carcinoma. Peripheral blood, spleen and tumor infiltrating cells were isolated from tumor bearing mice and compared to healthy controls by analysis of different populations of TIL by flow cytometry and immunohistochemistry. In parallel, patients derived tumor and blood samples were analyzed.

Results:

We observed considerable T- as well as B-cell-infiltrates. Detailed analyses revealed the existence of germinal center B cells as well as follicular T helper cells in spleens of tumor bearing mice. Moreover, the same B- and T cell-populations could be identified in tumor infiltrates of mice and patients indicating the appearance of germinal center like structures within the tumor. This observation could be validated in IHC studies. Additionally, we were also able to detect a massive increase of CD39+/CD73+ B cells in the blood and spleen of tumor bearing mice in comparison to their control counterparts.

Conclusion:

Although the role of TLS and its influence on the outcome of patients are still not completely understood, the analysis of different B cell populations in HNSCC mice and patients might be the founding stone for the development of new immuno-modulating therapeutic approach for HNSCC patients.

Publication History

Publication Date:
23 April 2019 (online)