title: Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8+ T cell immune response and antitumor effects in a preclinical cervical cancer model.
abstract: BACKGROUND
  Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA has been tested in a variety of preclinical models and in clinical trials and may be ideal for the treatment of cancer. However, it remains unclear how this treatment strategy affects the host immune response against tumors.
  
  
  RESULTS
  Here, we used a well-defined E6/E7-expressing tumor model to examine how the immune system can be motivated to act against tumor cells expressing tumor antigens. We demonstrate that the combination of bortezomib and SAHA elicits potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the first to show that treatment with bortezomib and SAHA leads to tumor-specific immunity by rendering tumor cells more susceptible to killing by antigen-specific CD8+ T cells than treatment with either drug alone.
  
  
  CONCLUSIONS
  The current study serves an important foundation for the future clinical application of both drugs for the treatment of cervical cancer.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. pyamyhuang@163.com.|Department of Gynecology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China. pyamyhuang@163.com.
authors.forename: Zhuomin
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. speng1@jhmi.edu.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. jayne.knoff@gmail.com.
authors.forename: Jayne
authors.initials: J
authors.lastname: Knoff
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. pusarang@gmail.com.|Department of Internal Medicine, Korea University Medical Center, Seoul, South Korea. pusarang@gmail.com.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. b.y.himself91@gmail.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. wutc@jhmi.edu.|Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. wutc@jhmi.edu.|Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. wutc@jhmi.edu.|Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. wutc@jhmi.edu.
authors.forename: Tzyy-Choou
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 307, 1550 Orleans Street, 21231, Baltimore, MD, USA. chung2@jhmi.edu.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000069286:Bortezomib / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D061988:Proteasome Inhibitors / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D061988:Proteasome Inhibitors; D000077337:Vorinostat; D000069286:Bortezomib