Spatial single-cell analysis reveals tumor microenvironment signatures predictive of oral cavity cancer outcome
: Näsiaho, Joni; Nissi, Linda; Ventelä, Sami; Irjala, Heikki; Salmi, Marko
Publisher: Elsevier BV
: 2026
Cell Reports Medicine
: 102615
: 7
: 2
: 2666-3791
DOI: https://doi.org/10.1016/j.xcrm.2026.102615
: https://doi.org/10.1016/j.xcrm.2026.102615
: https://research.utu.fi/converis/portal/detail/Publication/515723942
Up to 20% of patients with early-stage oral squamous cell carcinoma (OSCC) develop postoperative relapse, but no parameters currently enable the identification of individuals with poor prognosis. Here, we report a spatially resolved single-cell analysis of the tumor microenvironment in OSCC. By analyzing >700,000 cells for 25 proteins using imaging mass cytometry, we discover leukocyte and endothelial cell phenotypes that are independent prognostic factors for survival. Most notably, the presence of proliferating lymphatic endothelial cells (KI67+PROX1+), which show distinct molecular signature in transcriptomic analyses, in the invasive tumor margin strongly predicts poor recurrence-free survival in early-stage OSCC. We validate our findings in an independent OSCC cohort using an easy-to-measure KI67+PROX1+ immunostaining biomarker assay and multivariate analyses of recurrence-free, disease-specific, and overall survival. Thus, our data highlight the role of tumor microenvironment in OSCC progression and its potential impact on treatment strategies.
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We thank Auria Biobank for OSCC samples, Histocore for cutting sections, Turku Bioscience for IMC microscope facility, and CSC for supercomputer time. We thank Dr. Jutta Huvila for providing advice regarding OSCC histopathology. J.N. was financially supported by the TuDMM postgraduate school and the Research Council of Finland InFLAMES Flagship. M.S. obtained research funding from the Finnish Cancer Foundation, Sigrid Juselius Foundation, and InFLAMES Flagship; H.I. and S.V. from Kirsti and Tor Johanssons Hjärt och Cancerstiftelse sr and the State Research Fund for Southwest Welfare District; and S.V. from the Finnish Medical Foundation, Jane and Aatos Erkko Foundation, and the Research Council of Finland (#354599).
