Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. METHODS: We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. RESULTS: Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. CONCLUSION: The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.

Hyperion imaging system reveals heterogeneous tumor microenvironment of oral squamous cell carcinoma patients at T1N0M0 stage.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a highly heterogeneous neoplasm where the identification of heterogeneity is a critical clinical need to improve treatment planning and prognosis prediction. Utilizing the Hyperion imaging system to carry out high-dimensional proteomics analysis on the heterogeneity of tumor samples, this study aims to detect and analyze the heterogeneity of OSCC without lymph node metastasis and explore potential contributing factors for poor prognosis of early-stage OSCC. METHODS: We collected tumor tissue samples from four OSCC patients at the T1N0M0 stage, who presented with similar clinical manifestations. Patient formalin-fixed, paraffin-embedded (FFPE) tissue sections were prepared and stained using a panel of 26 immune or tumor-related antibodies. Different metal tags were assigned to each antibody. The stained cells were then detected and analyzed by the Hyperion imaging system. RESULTS: Tumor samples of four OSCC patients presenting with similar clinical characteristics at the T1N0M0 stage had different cell subtypes, including CD4+ T cells, CD8+ T cells, CD19+ B cells, CD11c+ dendritic cells, CD56+ natural killer cells, granulocytes, etc. More immunosuppressive cells were found in the sample of patient 1. We propose that differences in the tumor microenvironment of samples may contribute to different patients' prognosis in the future. CONCLUSIONS: High-dimensional proteomics analyses using the Hyperion imaging system help identify and analyze the tumor microenvironment heterogeneity of OSCC. Our study now presents this valuable resource and explains the potential reasons behind early OSCC patients' poor prognosis.

Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.