Session Item

Head and neck carcinomas comprise distinct tumor subtypes with heterogeneous responses to anticancer therapies. Risk profile markers for individualized therapy regimens are urgently needed. Besides established molecular markers, certain immune cell populations have been associated with clinical outcome. CD8+ T cells have emerged as key predictive and prognostic immune markers across various cancer types, including head and neck squamous cell carcinoma (HNSCC). Dendritic cells (DCs), which play major roles in T cell activation, have been positively correlated to survival when present at high densities within certain tumor types, such as colon carcinoma. In this study we aimed to assess the clinical relevance of certain CD8+ T cell phenotypes and DC subsets in HNSCC treated by radical resection and adjuvant irradiation.

This retrospective study comprised FFPE tumour specimens obtained by surgery from 59 patients with advanced HNSCC, that were stained by multiplex immunohistochemistry. Using antibodies against CD8, PD-1, LAG3, GrzB, and Ki67, as well as subset-specific markers for DCs, we evaluated the frequency and spatial distribution of CD8+ T cells (including all potential phenotypes) and DCs (cDC1s, cDC2s, and pDCs) across all tumors, as well as within certain specific HNSCC subgroups. Subsequently, potential correlations between immune cell related parameters and hypoxia-associated gene signatures, p53 and HPV status were examined. Additionally, we explored whether T cells and DC frequencies and phenotypes differed between subgroups of HNSCC (oropharyngeal only carcinomas, p16+ and p16- subgroups) and verified the potential links to clinical survival.

Significantly higher densities of CD8+ T cells (including their various phenotypes) and DC subsets were present in HPV-positive vs. negative tumors, but decreased in hypoxic vs. non-hypoxic tumors. In the whole cohort, an elevated frequency of CD8+ T cells was significantly associated with improved PFS, while in the oropharyngeal subgroup we determined a positive correlation between higher CD8+ and CD8+LAG3+ T cells densities and survival (both PFS and OS), as well as between higher type I cDCs density and LRFS. In the HPV-positive subcohort, a positive correlation with the OS by CD8+/PD1+ and CD8+/PD1+/Ki67+ and on the LRC by CD8+ cells was shown. Interestingly, in the HPV-negative subcohort, however, a significantly negative correlation with LRFS, PFS, OS by CD8+ T-cell phenotypes with expression of CD8, PD1, GrzB, LAG and Ki67 was found.

The frequency of certain CD8+ and DC phenotypes significantly associated with the clinical outcome in HNSCC after adjuvant radiation and could contribute to a further risk group classification, especially in HPV-negative tumors. The association between tumor immune architecture and tumor biology-related parameters potentially leads to the identification of novel predictive markers, that could lead to more individualized therapy regimens.