Distinct subpopulations of cancer associated fibroblasts in oral squamous cell carcinoma revealed by imaging mass cytometry.

Autor: Costea, S, Tornaas, DE, Kleftogiannis, D, Fromreide, S, Ytre-Hauge-Smeland, H, Aarstad, HJ, Vintermyr, OK, Akslen, LA, Dongre, HN
Zdroj: Oral Surgery, Oral Medicine, Oral Pathology & Oral Radiology; Jan2025, Vol. 139 Issue 1, pe33-e33, 1p
Abstrakt: Although cancer associated fibroblast (CAF) heterogeneity is recognized in oral squamous cell carcinoma (OSCC), the phenotype and role of CAF subpopulations in OSCC is still unknown. This study aimed to develop a method to identify and spatially define CAF subpopulations on formalin fixed paraffin embedded (FFPE) tissues from primary OSCC. Imaging mass cytometry was used to identify 24 markers (E-cadherin, EGFR, Ki-67, α-SMA, CD140β, FAP, FSP-1/S100A4, CD90/Thy-1, integrin α-11, collagen-1, tenascin-C, caveolin-1, CD4, CD8a, CD16, CD20, CD68, CD163, FoxP3, granzyme B, CD31, podoplanin, CD146, and YAP-1) in HPV-negative OSCC lesions (n=5). Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R language. Unsupervised clustering identified several major cell types, with E-cadherin+ cells being the most abundant (30% and CD146+ being the least abundant cell type (0.62%). Among the immune component, CD4+ were most abundant (11.72%) followed by CD8+ (10.6%) and CD68+ (10.25%). Two clusters were negative for other major lineage markers and positive for stromal markers. These were defined as CAF-1 (high αSMA, CD140β, and CD90) and CAF-2 (high FAP and collagen-1). CAF-1 subtype was found closer to immune cells whereas CAF-2 were closely located to cancer cells. Based on integrin α-11, FSP-1/S100A4 and podoplanin these could be further dissected in 6 CAF clusters. The pipeline developed here shows promise for understanding clinical implications of CAF heterogeneity in clinical samples from large OSCC patient cohorts with FFPE tissues available in diagnostic biobanks. [ABSTRACT FROM AUTHOR]
Databáze: Supplemental Index