Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma

SIMPLE SUMMARY: In head and neck squamous cell carcinoma (HNSCC), a major challenge with treatments targeting the immune system is an incomplete understanding of rare immune cell subtypes. Several recent studies have explored these cell types, but these studies have not integrated cellular data with clinicopathologic or demographic features to place conclusions in an appropriate clinical context. We deconvolve transcriptomic data from HNSCC patients to infer proportions of immune cell subtypes and place these data in the context of demographic, clinical, pathologic, and genomic characteristics. Our analysis revealed a possible association of γδ T cells with poor survival in HNSCC and underscore the need to better understand the role of these rare cells in HNSCC, including whether the presence of γδ T cells may predict the need for adjuvant therapy. ABSTRACT: (1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.