However, the impact of the tumor immune microenvironment on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) remains unclear. Using multiparameter imaging and mass cytometry, researchers compared the immunological microenvironment of high-risk HNcSCC that did not metastasize with that of HNcSCC that did. Immunosuppressed (IS) patients and patients without clinical immune-suppression (ACIS) were included in the cohort. 

Researchers employed spatial analysis to find cellular connections that predicted tumor behavior. Higher CD8+ and CD4 + T-cell responses, as well as an increase in the number of regulatory T cells, were found in patients with initial HNcSCC that did not advance. However, metastatic lesions from HNcSCC patients were characterized by an excess of B cells, while original lesions from these patients were largely devoid of T cells, with fewer numbers of innate immune cells and greater expression of checkpoint receptors. A spatial examination of primary tumors from individuals whose disease is not progressing reveals many cellular interactions unique to these malignancies. 

Primary tumors that are not progressing can be identified by their cellular regional analysis, which reveals that these tumor regions are concentrated in squamous cells. Tumor-specific CD8+ and CD4+ T cell responses in the microenvironment of initial HNcSCC tumors are required for immunological control. This data suggested that the course and fate of HNcSCC are determined by the initial events that shape the immune responses in primary tumors.