Primary and local recurrent head and neck squamous cell carcinomas are strikingly different regarding their immune microenvironment

Background Tumor immune microenvironment (TIME) has a crucial impact on cancer progression and survival for various cancer entities. In head and neck squamous cell carcinoma (HNSCC) the development of recurrences in up to 60 % is one main factor leading to poor prognosis. We aimed to reveal changes in the TIME of primary tumours and their corresponding recurrences.

Design The TIME of 70 formalin fixed paraffin embedded (FFPE) tissue samples of HNSCC primary tumours and their corresponding local recurrences was characterised via immunohistochemical staining for the markers CD4, CD8, CD20, FOXP3, CD1A, PD1, CD68 and CD56 .The RNA of a subgroup of 18 patients, who underwent (chemo-)radiation therapy between the resection of the primary tumour and the development of a local recurrence, expression levels of 770 immune related genes were identified by nanostring and assessed with the nSolver™ Analysis Software.

Results The immunohistochemical TIME analysis showed a loss of B lymphocytes (p = 0.0006), an increase in dendritic cells (p= 0.017) and a decrease in the CD8/FOXP3 T-cell ratio (p= 0.106) in HNSCC recurrences compared to their corresponding primary tumours. RNA analysis confirmed the depletion of B lymphocytes and revealed a strong decrease in the total number of tumor infiltrating lymphocytes (TILs) as well as an increase in dendritic cells, mast cells, neutrophils and macrophages in HNSCC recurrences. Significantly downregulated chemokines included CXCL13 and CXCR5, involved in B lymphocyte chemotaxis.

Conclusion Our results reveal significant differences in the TIME of HNSCC primary tumours and recurrences, characterised by loss of B lymphocytes and an overall shift from anti-tumor immune response to an increase in pro-tumor immune factors in recurrences.

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Artikel online veröffentlicht:
10. Juni 2020