Local Low-dose Anti-PD-L1 Antibodies Improve Antitumor Effects in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors are highly effective for treating recurrent and metastatic head and neck cancers. However, they require systemic administration and are associated with immune-related adverse events (irAEs). Reducing therapeutic antibody doses to prevent irAEs is challenging. MATERIALS AND METHODS: Mouse buccal mucosa squamous cell carcinoma cells (Sq-1979) were transplanted into the backs of mice to induce tumors. The antitumor efficacy and tumor immunohistological environment in tumor-bearing mice were compared after administering a standard dose of programmed death-ligand 1 (PD-L1) antibodies systemically (200 mg/body) or 1/10th of the standard dose (20 mg/body) directly to tumors. Mice received four doses of antibody administered in 3-day intervals. Tumor reduction rates and antitumor efficacies were evaluated 21 days after initiating treatment. CD8+T cell counts and PD-L1, PD-1, perforin, and granzyme B levels; CD25 and Foxp3 expression levels; and tumor Tregs were assessed in the resected subcutaneous tumors. RESULTS: The antitumor efficacies in the local low-dose and systemic standard-dose groups were compared with that of the control group. The efficacies of the two treatment groups were similar, and both treatment groups revealed significant antitumor effects compared to the control group. Perforin and granzyme B levels were higher in the local low-dose group (p<0.05). CONCLUSION: Local low-dose administration of anti-PD-L1 antibodies exhibits antitumor efficacy similar to systemic standard-dose administration suggesting that local low-dose administration is useful for treating oral squamous cell carcinoma.

The ECAS system can superselectively administer anticancer drugs to numerous feeding arteries from the superficial temporal artery: A case report and literature review.

Superselective intra-arterial chemoradiotherapy (SSIACRT) is one of the curative treatments for advanced oral cancer. SSIACRT can reportedly treat cervical lymph node metastases in the level I-IIA area by super selectively catheterizing the facial artery (FA) and infusing drugs. However, since advanced oral cancer lesions involve a number of feeding vessels, retrograde treatment requires the placement of catheters from the superficial temporal artery (STA) and occipital artery (OA). Furthermore, in the case of level IIB lymph node metastasis, the catheter must be changed because it is necessary to administer anticancer drugs to more than three routes, including the OA, when the feeding arteries of the primary tumor are combined. The external carotid artery sheath (ECAS) system used in the present study involves the insertion of a microcatheter or steering catheter from one route of the STA, allowing selection of numerous feeding vessels, including the OA. The ECAS system can facilitate the administration of chemotherapy via the STA simultaneously to the maxillary artery, lingual artery, FA and OA. The present study describes cases of maxillary gingival cancer and tongue cancer with cervical lymph node metastasis, which were treated with the ECAS system via the STA; the treatment successfully controlled both the primary tumor and cervical lymph node metastasis. In the two cases described in the present study, metastatic lymph nodes were found in the level ⅠB and ⅡB region, but were successfully treated by administering cisplatin via the OA, in addition to the primary lesion. To date, to the best of our knowledge, there is no case report clearly referring to the treatment of lymph node metastasis using the ECAS system. In conclusion, SSIACRT using ECAS may be considered a useful treatment for oral cancer with cervical lymph node metastasis.