Open AccessA combination of anti‐ PD ‐L1 mA b plus Lm‐ LLO ‐E6 vaccine efficiently suppresses tumor growth and metastasis in HPV ‐infected cancers
Author(s) -
Lin PoLin,
Cheng YaMin,
Wu DeWei,
Huang YuJu,
Lin HunChi,
Chen ChihYi,
Lee Huei
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1143
Subject(s) - immunohistochemistry , cancer research , immune system , immunotherapy , lung cancer , metastasis , medicine , cancer , immunology
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. 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. Immune deficiency nude mice were used to test the possibility that combining anti‐ PD ‐L1 mA b with Lm‐ LLO ‐E6 vaccine could have a higher antitumor activity compared with anti‐ PD ‐L1 mA b or Lm‐ LLO ‐E6 vaccine alone. A greater antitumor activity was obtained with anti‐ PD ‐L1 mA b + Lm‐ LLO ‐E6 vaccine than with anti‐ PD ‐L1 mA b 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 mA b + Lm‐ LLO ‐E6 vaccine group. In conclusion, an anti‐ PD ‐L1 mA b + Lm‐ LLO ‐E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV ‐infected cells.