A combination of anti-PD-L1 mAb plus Lm-LLO-E6 vaccine to suppress tumor growth and metastasis in HPV-infected cancers.

e23175 Background: PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy for certain non-small cell lung cancer (NSCLC) patients. Methods: PD-L1 and E6 oncoprotein expressions in lung tumors from 122 NSCLC patients were examined by immunohistochemistry and their prognostic value was evaluated by Kaplain-Meier and Cox regression analysis. HPV16-postive and negative TL-1 and TL-4 lung cancer and SiHa and C33A cervical cancer cells were used to test whether PD-L1 expression could be regulated by E6, not by E7 oncoprotein. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. Results: Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. A greater antitumor activity was obtained with anti-PD-L1 mAb+Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb+Lm-LLO-E6 vaccine group. Conclusions: An anti-PD-L1 mAb+Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.