Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Biomed Res Int. 2021 Jul 2;2021:5568428. doi: 10.1155/2021/5568428. eCollection 2021.
In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors.
Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining.
Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO-treated and combination groups.
It was confirmed that the tumour immunosuppressive factors decreased due to local CO administration to the mouse model. CO administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.
近年来，肿瘤免疫抑制机制已成为肿瘤化疗耐药性的一个原因而受到关注。虽然已经报道肿瘤的化疗耐药性和免疫抑制与缺氧环境有关，但尚未建立改善肿瘤缺氧的有效治疗方法。我们之前已经将二氧化碳（CO）应用于鳞状细胞癌，并表明改善局部氧合具有抗肿瘤作用。然而，局部 CO 给药对肿瘤免疫抑制、化疗耐药性以及与化疗联合应用的效果尚不清楚。在这项研究中，我们研究了局部 CO 给药对鳞状细胞癌的影响以及与化疗联合应用的效果，重点关注对肿瘤免疫抑制因子的影响。
将人口腔鳞状细胞癌（HSC-3）皮下移植到裸鼠背部，并给予 CO 和顺铂。给药 4 次，每周 2 次后，收集肿瘤并使用实时聚合酶链反应和免疫组化评估肿瘤免疫抑制因子（PD-L1、PD-L2 和半乳糖凝集素-9）的表达。
与对照组相比，CO 治疗组和联合治疗组的 PD-L1 mRNA 表达均显著降低。同样，CO 治疗组和联合治疗组的 PD-L2 和半乳糖凝集素-9 的表达也降低。此外，免疫组化也显示 CO 治疗组和联合治疗组肿瘤免疫抑制因子的蛋白表达显著降低。
证实了由于向小鼠模型局部给予 CO，肿瘤免疫抑制因子减少。CO 给药有可能改善肿瘤的缺氧环境，与化疗联合使用也可能改善肿瘤免疫抑制。
