Tissue resident memory T cells (TRM) in primary, metastatic and recurrent head and neck squamous cell carcinoma (HNSCC) tissue

Introduction High numbers of tumour infiltrating lymphocytes (TIL) are known to link to better survival in cancer patients. TRM (CD8+CD103+) are a TIL subgroup and are recognised as a key player of anti-cancer immune response. To assess TRM in primary, metastatic, and recurrent HNSCC tissue we developed a tissue microarray (TMA) and used multiplex immunohistochemistry (MxIHC).

Material and Methods HNSCC cases of the Southampton Hospital were searched between 2000 and 2016 and approximately 300 cases with adequate material of primary tumours were found. Of these, 100 cases had lymph node metastases, and 80 had at least one recurrence. A TMA was generated after marking the tumour areas of all slides with triplicates of cores. Following, a MxIHC with a stain, scan, and strip approach was done using inter alia CD8, TIM-3, and CD103. The scanned slides were analysed using digital image analysis software and a quality check (QC) was performed.

Results After the QC we had 194 primary tumours, 76 lymph node metastases, and 65 recurrence samples. We found significantly more CD8 T cells in the lymph node metastasis, while the TRM infiltration was the same. TIM3, as an exhaustion marker, was significantly higher expressed on TRM and non-TRM T cells in the lymph node compared to the primary tumour. The TIM3 expression was also significantly higher on TILs in the recurrences. Lastly, we saw the known survival benefit of TRM infiltration in the primary tumours, however, this was not the case for the lymph node metastasis.

Conclusion We describe the importance of TRM in primary, metastatic and recurrent HNSCC and the influence on survival. TIM3 could reduce the positive effect of TRM as an exhaustion marker and highlights its possible status as a new immunotherapeutic target.

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Artikel online veröffentlicht:
24. Mai 2022