Trumet Leah, Ries Jutta, Sobl Philip, Ivenz Niclas, Wehrhan Falk, Lutz Rainer, Kesting Marco, Weber Manuel
Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Cancers (Basel). 2023 Jul 25;15(15):3755. doi: 10.3390/cancers15153755.
There is increasing evidence of the benefits of adjuvant and neoadjuvant immunotherapy in the treatment of solid malignancies like oral squamous cell carcinoma (OSCC). To optimize (neo-)adjuvant treatment, the systemic immunomodulatory effects of tumor surgery itself need to be considered. Currently, there is little evidence on the immunological effects of major surgery, such as free microvascular flap reconstruction. The current study aims to analyze how and to what extent maxillofacial surgery affects systemic parameters of immune tolerance.
A total of 50 peripheral whole blood samples from patients (Group 1 (G1) = extensive OSCC surgery; Group 2 (G2) = free flap reconstruction without persistent malignant disease; Group 3 (G3) = minor maxillofacial surgery) undergoing surgery were included for real-time quantitative polymerase chain reaction (RT-qPCR) to examine changes in mRNA expression of the biomarkers IL-6, IL-10, FOXP3, and PD-L1. Blood samples were taken immediately before and after surgery as well as on the second, fourth, and tenth postoperative days. Differences in mRNA expression between groups and time points were calculated using statistical tests, including Mann-Whitney U-test and Pearson correlation analysis.
Comparing postoperative expression of G1 and G3, there was a significantly higher PD-L1 expression ( = 0.015) in G1 compared to G3 and a significantly lower IL-6 ( = 0.001) and FOXP3 ( = 0.016) expression. Interestingly, IL-10 expression was higher pre- (0.05) and postoperative ( < 0.001) in G1 compared to G3. Additionally, in G1, there was a significant overexpression of IL-10 post-surgery compared to the preoperative value ( = 0.03) and a downregulated expression of FOXP3 between pre- and 2 d post-surgery ( = 0.04). Furthermore, there was a significant correlation between the duration of surgery and the perioperative expression changes of the analyzed biomarkers. As the duration of surgery increased, the expression of IL-10 and PD-L1 increased, and the expression of IL-6 and FOXP3 decreased.
Extensive surgery in OSCC patients is associated with a transient shift toward postoperative systemic immune tolerance compared with patients undergoing minor surgery. However, even extensive surgery causes no signs of long-lasting systemic immunosuppression. The degree of immune tolerance that occurred was associated with the duration of surgery. This supports efforts to minimize the duration of surgery.
越来越多的证据表明，辅助和新辅助免疫疗法在治疗口腔鳞状细胞癌（OSCC）等实体恶性肿瘤方面具有益处。为了优化（新）辅助治疗，需要考虑肿瘤手术本身的全身免疫调节作用。目前，关于诸如游离微血管皮瓣重建等大型手术的免疫效应的证据很少。本研究旨在分析颌面外科手术如何以及在多大程度上影响免疫耐受的全身参数。
纳入50例接受手术的患者的外周全血样本（第1组（G1）=广泛的OSCC手术；第2组（G2）=无持续性恶性疾病的游离皮瓣重建；第3组（G3）=小型颌面外科手术），用于实时定量聚合酶链反应（RT-qPCR），以检测生物标志物白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、叉头框蛋白P3（FOXP3）和程序性死亡受体配体1（PD-L1）的mRNA表达变化。在手术前、手术后以及术后第2天、第4天和第10天采集血样。使用包括曼-惠特尼U检验和皮尔逊相关分析在内的统计检验计算组间和时间点之间mRNA表达的差异。
比较G1组和G3组的术后表达，G1组的PD-L1表达显著高于G3组（P = 0.015），而IL-6（P = 0.001）和FOXP3（P = 0.016）表达显著低于G3组。有趣的是，与G3组相比，G1组术前（P = 0.05）和术后（P < 0.001）的IL-10表达更高。此外，在G1组中，术后IL-10表达相对于术前值显著上调（P = 0.03），并且术前与术后第2天之间FOXP3表达下调（P = 0.04）。此外，手术持续时间与所分析生物标志物的围手术期表达变化之间存在显著相关性。随着手术持续时间的增加，IL-10和PD-L1的表达增加，而IL-6和FOXP3的表达降低。
与接受小型手术的患者相比，OSCC患者的广泛手术与术后全身免疫耐受的短暂转变有关。然而，即使是广泛手术也未出现长期全身免疫抑制的迹象。发生的免疫耐受程度与手术持续时间有关。这支持了尽量缩短手术时间的努力。
