WEN-FANG CHENGLI-KUEI CHENCHI-AN CHENChang M.-C.PO-NI HSIAOSu Y.-N.CHIEN-NAN LEEJeng H.-J.CHANG-YAO HSIEHWEI-ZEN SUN2020-02-142020-02-1420061525-00162-s2.0-28844506819https://scholars.lib.ntu.edu.tw/handle/123456789/458658Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found that morphine-injected mice exhibited higher tumor growth rates and lower percentages of CD8+ T lymphocytes. The mechanism of morphine suppression of immunity might be through the suppression of E7-specific CD8+ T lymphocyte proliferation and the promotion of apoptosis of these cells by the Bcl-2 and Bax pathways. The suppressive effect of E7-specific CD8+ T lymphocytes by morphine could be reversed by naloxone. We have previously shown that calreticulin linked with E7 (CRT/E7) could enhance the CD8+ T cell response and the anti-tumor effects (W. F. Cheng et al. (2001) J. Clin. Invest. 108, 669-678). CRT/E7 DNA vaccine could overcome the immunosuppressive effect of morphine and suppress tumor growth. Our findings reveal that long-term morphine treatment dose-dependently promotes tumor growth and a DNA vaccine may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment. Copyright ? The American Society of Gene Therapy.[SDGs]SDG3calreticulin; CD8 antigen; DNA vaccine; morphine sulfate; naloxone; protein Bax; protein bcl 2; protein E7; T lymphocyte antigen; animal cell; animal experiment; animal model; apoptosis; article; cancer inhibition; carcinogenesis; cellular immunity; chimera; controlled study; dose response; drug mechanism; female; immune deficiency; long term care; mouse; nonhuman; T lymphocyte; Analgesics, Opioid; Animals; Apoptosis; bcl-2-Associated X Protein; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Female; Immunosuppression; Mice; Mice, Inbred C57BL; Morphine; Narcotic Antagonists; Neoplasm Transplantation; Neoplasms, Experimental; Papillomavirus E7 Proteins; Proto-Oncogene Proteins c-bcl-2; Transplantation, Heterologous; Vaccination; Vaccines, DNA; Animaliajournal article10.1016/j.ymthe.2005.06.47956601533000