High-Dimensional and Spatial Analysis Reveals Immune Landscape-Dependent Progression in Cutaneous

Purpose: The tumor immune microenvironment impacts the biological behavior of the tumor, but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown.Experimental Design: We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasized using multiparameter imaging mass cytometry. The cohort included both immunosuppressed patients (IS) and patients with an absence of clinical immune-suppression (ACIS). Spatial analyses were used to identify cellular interactions that were associated with tumor behavior.Results: Nonprogressing primary HNcSCC were characterized by higher CD8 thorn and CD4 thorn T-cell responses, including numerically increased regulatory T cells. In contrast, primary lesions from HNcSCC patients who progressed were largely devoid of T cells with lower numbers of innate immune cells and increased expres-sion of checkpoint receptors and in the metastatic lesions were characterized by an accumulation of B cells. Spatial analysis reveals multiple cellular interactions associated with nonprogressing pri-mary tumors that were distinct in primary tumors of disease -progressing patients. Cellular regional analysis of the tumor micro -environment also shows squamous cell-enriched tumor regions associated with primary nonprogressing tumors.Conclusions: Effective responses from both CD8 thorn and CD4 thorn T cells in the tumor microenvironment are essential for immune control of primary HNcSCC. Our findings indicate that the early events that shape the immune responses in primary tumors dictate progression and disease outcomes in HNcSCC.

Automated summary

The tumor immune microenvironment plays a significant role in the clinical outcomes of head and neck cutaneous squamous cell carcinomas (HNcSCC). This study compared the immune milieu of high-risk HNcSCC that did not progress to metastasis with those that did, using multiparameter imaging mass cytometry. The findings suggest that effective immune responses from CD8 and CD4 T cells are crucial for controlling primary HNcSCC, and early events that shape the immune responses in primary tumors dictate disease progression and outcomes in HNcSCC.