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

AI Article Synopsis

  • The study explores how the immune microenvironment affects the behavior and clinical outcomes of head and neck cutaneous squamous cell carcinomas (HNcSCC), particularly comparing tumors that do not metastasize to those that do.
  • It utilizes advanced imaging techniques to analyze the immune cell composition and spatial relationships within tumors from both immunosuppressed patients and those without clinical immune suppression.
  • Results indicate that successful immune responses involving CD8+ and CD4+ T cells are linked to non-progressing tumors, whereas tumors that progress exhibit fewer T cells, more checkpoint receptors, and a higher presence of B cells, highlighting the importance of the immune response in determining tumor outcomes.

Article Abstract

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.

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Source
http://dx.doi.org/10.1158/1078-0432.CCR-22-1332DOI Listing

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