Transcutaneous Carbon Dioxide Decreases Immunosuppressive Factors in Squamous Cell Carcinoma In Vivo

Abstract

Introduction. 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 (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. Methods. Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 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. Results. Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. Conclusion. It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.

Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model

“…Treatment was commenced twice a week for 3 weeks, starting 7 d after the injection. Referring to our previous studies, the endpoint was set at 25 d after injection [19,20]. Tumor growth and body weight were measured on each day of treatment.…”

The Tissue Response to Hypoxia: How Therapeutic Carbon Dioxide Moves the Response toward Homeostasis and Away from Instability

“…There are now many more methods for using therapeutic CO 2 . Such treatment regimens used today include carbonated water (i.e., baths) (CB) [ 6 ], CO 2 gas applied to the skin (transdermal [TD]) [ 7 , 8 ], intra-arterial infusions of carbonated solutions into tumors (IA) [ 9 ], intraperitoneal injection of CO 2 (IP) [ 10 ], inhaled CO 2 or hypercarbia (IH) [ 11 ], carbonated paste or gel (CG) [ 12 ], and subcutaneous microinjections of CO 2 (SQ) [ 13 ]. In all these therapeutic applications, except for SQ, CO 2 is applied for 10–20 min.…”

Local application of a transcutaneous carbon dioxide paste prevents excessive scarring and promotes muscle regeneration in a bupivacaine‐induced rat model of muscle injury

“…Therefore, we developed a topical cutaneous CO 2 paste that generates CO 2 within the material by reacting with moisture on the skin's surface and efficiently absorbs CO 2 from the skin. 12 , 13 …”

“…Previous studies have used gaseous CO 2 , but this is not applicable to the head and neck regions. Therefore, we developed a topical cutaneous CO 2 paste that generates CO 2 within the material by reacting with moisture on the skin's surface and efficiently absorbs CO 2 from the skin 12,13 …”

“…Therefore, we developed a topical cutaneous CO 2 paste that generates CO 2 within the material by reacting with moisture on the skin's surface and efficiently absorbs CO 2 from the skin. 12,13 Here, our aim was to investigate whether the CO 2 paste could prevent excessive scarring and promote muscle regeneration. To that aim, we used a bupivacaineinduced rat model of muscle injury and performed gene expression analysis and immunohistochemistry.…”