The tumour microenvironment of Mucosal Head and Neck Squamous Cell Carcinoma and its influence on immune checkpoint inhibitor response

Abstract

Mucosal Head and Neck Squamous Cell Carcinoma (mHNSCC) is cancer arising from the epithelium of the upper aerodigestive tract and is the sixth most common cancer globally. The last decade has seen immune checkpoint inhibitors (ICI) become a viable therapy for patients with many solid tumours. mHNSCC patients treated with PD-1 ICIs have demonstrated response rates of approximately 20% and 12-month progression free survival of 20%. For these patients who have exhausted other options, ICI therapy can provide improved length and quality of survival. Identifying the patients who will benefit from these treatments the challenge. The answers may lie in the Tumour Microenvironment (TME).

In this study, Imaging Mass Cytometry (IMC) was used to enhance the understanding of the mHNSCC TME and the role it plays in response to PD-1 ICI. IMC permits simultaneous quantification of cells in a tissue, their activation status, functional potential and analysis of spatial interactions between different cells within the TME.

We identified significantly higher infiltrates of proliferating CD4+ T cells and CD44+ NK cells in patients who failed to respond to PD-1 ICI. Other immune cell phenotypes such as HLA-ABC+ CD8+ T cells and PD1+ Central Memory CD8+ T cells were also found to be significantly increased in patients who responded to PD-1 ICI. Key spatial interactions between several unique subsets of immune and tumour cells in patients who failed to respond to PD-1 ICI were identified. These interactions included specific CD4+ Regulatory T cells, granulocyte, monocyte-derived immune cells and SCC cells and may represent mechanisms for resistance to PD-1 ICI in patients who fail to respond to treatment. These findings signify an important early step in identifying potential mechanisms for PD-1 ICI treatment resistance, identification of potential therapeutic targets for investigation and prognostic markers for future patients receiving a mHNSCC diagnosis.