Trumet Leah, Weber Manuel, Hahn Alina, Kunater Lina, Geppert Carol, Glajzer Jacek, Struckmeier Ann-Kristin, Möst Tobias, Lutz Rainer, Kesting Marco, Ries Jutta
Department of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Department of Operative Dentistry and Periodontology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Cancers (Basel). 2023 Apr 2;15(7):2126. doi: 10.3390/cancers15072126.
: As immunotherapy of oral squamous cell carcinomas (OSCCs), using PD1 inhibitors, is only efficient in a small proportion of patients, additional immune checkpoints need to be identified as potential therapeutic targets. There is evidence that a blockade of CD96 might positively affect the anti-tumor immune response. The aim of this study was to analyze the gene and protein expression of CD96 in the tissue and peripheral blood of OSCC patients compared to healthy controls, while also checking for potential associations with a differential expression to the histomorphological parameters. In addition, possible correlations with the expression of PD1 and PD-L1 as well as the macrophage markers CD68 and CD163 should be tested to obtain further insights into the potential effectiveness of combined checkpoint blockage. For real-time quantitative polymerase chain reaction (RT-qPCR), a total of 183 blood and tissue samples, divided into a patient and a control group, were included. Additionally, 141 tissue samples were examined by immunohistochemistry (IHC). The relative expression differences between the groups were calculated using statistical tests including the Mann-Whitney U test and AUC method. The Chi-square test was used to determine whether CD96 overexpression in individual samples is associated with malignancy. Correlation analysis was performed using the Spearman correlation test. There was a significant CD96 mRNA and protein overexpression in the OSCC group compared to the controls ( = 0.001). In contrast, CD96 mRNA expression in the peripheral blood of the OSCC patients was significantly lower compared to the control group ( = 0.007). In the Chi-square test, the OSCC tissue samples showed a highly significant upregulation of CD96 mRNA expression ( < 0.001) and protein expression ( = 0.005) compared to the healthy mucosa. CD96 mRNA and protein expression correlated significantly ( = 0.005). In addition, there was a significant positive correlation of CD96 expression with PD1 ( ≤ 0.001), PD-L1 ( ≤ 0.001), and CD163 ( = 0.006) at the mRNA level. CD96 expression in the tumor tissue and peripheral blood of OSCC patients is differentially regulated and appears to be a relevant immune checkpoint.
作为口腔鳞状细胞癌（OSCC）的免疫疗法，使用PD1抑制剂仅对一小部分患者有效，因此需要确定其他免疫检查点作为潜在的治疗靶点。有证据表明，阻断CD96可能会对抗肿瘤免疫反应产生积极影响。本研究的目的是分析OSCC患者组织和外周血中CD96的基因和蛋白表达，并与健康对照进行比较，同时检查其与组织形态学参数差异表达的潜在关联。此外，应测试与PD1和PD-L1表达以及巨噬细胞标志物CD68和CD163的可能相关性，以进一步了解联合检查点阻断的潜在有效性。对于实时定量聚合酶链反应（RT-qPCR），共纳入183份血液和组织样本，分为患者组和对照组。此外，对141份组织样本进行了免疫组织化学（IHC）检查。使用包括曼-惠特尼U检验和AUC法在内的统计检验计算组间的相对表达差异。卡方检验用于确定个体样本中CD96过表达是否与恶性肿瘤相关。使用Spearman相关检验进行相关性分析。与对照组相比，OSCC组中CD96 mRNA和蛋白有显著过表达（P = 0.001）。相反，OSCC患者外周血中CD96 mRNA表达与对照组相比显著降低（P = 0.007）。在卡方检验中，与健康黏膜相比，OSCC组织样本中CD96 mRNA表达（P < 0.001）和蛋白表达（P = 0.005）有高度显著上调。CD96 mRNA和蛋白表达显著相关（P = 0.005）。此外，在mRNA水平上，CD96表达与PD1（P ≤ 0.001）、PD-L1（P ≤ 0.001）和CD163（P = 0.006）有显著正相关。OSCC患者肿瘤组织和外周血中的CD96表达受到不同调节，似乎是一个相关的免疫检查点。
