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

Clin Cancer Res. 2022 Nov 1;28(21):4677-4688. doi: 10.1158/1078-0432.CCR-22-1332.


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+ and CD4+ 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 expression 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 primary tumors that were distinct in primary tumors of disease-progressing patients. Cellular regional analysis of the tumor microenvironment also shows squamous cell-enriched tumor regions associated with primary nonprogressing tumors.

Conclusions: Effective responses from both CD8+ and CD4+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Head and Neck Neoplasms*
  • Humans
  • Skin Neoplasms* / pathology
  • Spatial Analysis
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Microenvironment