Ekstedt Sandra, Cardenas Eduardo I, Piersiala Krzysztof, Liljeström Vilma, Petro Marianne, Ezerskyte Monika, Farrajota Neves da Silva Pedro, Kumlien Georén Susanna, Cardell Lars-Olaf
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.
Clin Exp Metastasis. 2025 Jun 23;42(4):37. doi: 10.1007/s10585-025-10356-z.
Neutrophil infiltration in tumors and tumor-draining lymph nodes (TDLNs) influences oral squamous cell carcinoma (OSCC) progression and metastasis. Neutrophils can exhibit an immunosuppressive phenotype, with CD18 and CD36 potentially linked to this. This study characterizes CD18/CD36 expression on neutrophils from different OSCC microenvironments and their association with metastasis.
We assessed CD18 and CD36 expression on neutrophils from OSCC tumors, TDLNs, and healthy lymph nodes using flow cytometry. We also examined whether co-culture with the CAL27 oral cancer cell line influenced CD18/CD36 expression in blood neutrophils from healthy donors.
Neutrophils from OSCC tumors and TDLNs exhibited higher CD18 expression than those from healthy lymph nodes, while CD36 was increased only in OSCC tumors. The highest CD18/CD36 expression was observed in metastasis. In vitro co-culture with CAL27 cells prolonged neutrophil survival and enhanced CD18 expression but had no impact on CD36 levels.
Increased CD18/CD36 expression in OSCC neutrophils, particularly in metastasis, suggests their role in tumorigenesis. The elevated CD18 expression in TDLNs highlights enhanced neutrophil-lymphocyte interactions during cancer progression. Our in vitro findings underscore the ability of cancer cells to modulate neutrophil lifespan and phenotype, though this may not fully replicate the tumor microenvironment. This study provides insight into neutrophil contributions to OSCC progression and supports their potential as therapeutic targets.
肿瘤及肿瘤引流淋巴结（TDLN）中的中性粒细胞浸润会影响口腔鳞状细胞癌（OSCC）的进展和转移。中性粒细胞可表现出免疫抑制表型，CD18和CD36可能与此有关。本研究对来自不同OSCC微环境的中性粒细胞上CD18/CD36的表达及其与转移的关系进行了表征。
我们使用流式细胞术评估了OSCC肿瘤、TDLN和健康淋巴结中中性粒细胞上CD18和CD36的表达。我们还研究了与CAL27口腔癌细胞系共培养是否会影响健康供体血液中性粒细胞中CD18/CD36的表达。
OSCC肿瘤和TDLN中的中性粒细胞比健康淋巴结中的中性粒细胞表现出更高的CD18表达，而CD36仅在OSCC肿瘤中增加。转移灶中观察到最高的CD18/CD36表达。与CAL27细胞的体外共培养延长了中性粒细胞的存活时间并增强了CD18表达，但对CD36水平没有影响。
OSCC中性粒细胞中CD18/CD36表达增加，尤其是在转移灶中，表明它们在肿瘤发生中的作用。TDLN中CD18表达升高突出了癌症进展过程中中性粒细胞与淋巴细胞相互作用的增强。我们的体外研究结果强调了癌细胞调节中性粒细胞寿命和表型的能力，尽管这可能无法完全复制肿瘤微环境。本研究为中性粒细胞对OSCC进展的贡献提供了见解，并支持它们作为治疗靶点的潜力。
