Combination of Proteasome and HDAC Inhibitor Enhances HPV16 E7-specific CD8+ T Cell Immune Response and Antitumor Effects in a Preclinical Cervical Cancer Model

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2015 Jan 17

PMID 25591912

Citations 14

Authors

ZhuoMin Huang

Shiwen Peng

Jayne Knoff

Sung Yong Lee

Benjamin Yang

Tzyy-Choou Wu

Chien-Fu Hung

Affiliations

Soon will be listed here.

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.

Citing Articles

Recombinant adenoviruses expressing HPV16/18 E7 upregulate the HDAC6 and DNMT3B genes in C33A cells.

Shao Y, Shah P, Su Q, Li S, Huang F, Wang J Front Cell Infect Microbiol. 2024; 14:1459572.

PMID: 39411320 PMC: 11473514. DOI: 10.3389/fcimb.2024.1459572.

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Zhou J, Xu L, Zhou H, Wang J, Xing X Genes (Basel). 2023; 14(7).

PMID: 37510286 PMC: 10379127. DOI: 10.3390/genes14071381.

Preclinical investigation of patient-derived cervical cancer organoids for precision medicine.

Seol H, Oh J, Choi E, Kim S, Kim H, Nam E J Gynecol Oncol. 2023; 34(3):e35.

PMID: 36659831 PMC: 10157333. DOI: 10.3802/jgo.2023.34.e35.

Pentraxin 3 Facilitates Shrimp-Allergic Responses in IgE-Activated Mast Cells.

Du J, Lai H, Hsiao Y, Chi J, Wang J J Immunol Res. 2022; 2022:8953235.

PMID: 36530573 PMC: 9750785. DOI: 10.1155/2022/8953235.

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy.

Sun X, Shu Y, Ye G, Wu C, Xu M, Gao R Acta Pharm Sin B. 2022; 12(2):838-852.

PMID: 35256949 PMC: 8897022. DOI: 10.1016/j.apsb.2021.07.003.

References

Asklund T, Kvarnbrink S, Holmlund C, Wibom C, Bergenheim T, Henriksson R . Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors. Anticancer Res. 2012; 32(7):2407-13. View

Campbell R, Sanchez E, Steinberg J, Shalitin D, Li Z, Chen H . Vorinostat enhances the antimyeloma effects of melphalan and bortezomib. Eur J Haematol. 2009; 84(3):201-11. DOI: 10.1111/j.1600-0609.2009.01384.x. View

Magner W, Kazim A, Stewart C, Romano M, Catalano G, Grande C . Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors. J Immunol. 2000; 165(12):7017-24. DOI: 10.4049/jimmunol.165.12.7017. View

Lin Z, Bazzaro M, Wang M, Chan K, Peng S, Roden R . Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment. Clin Cancer Res. 2009; 15(2):570-7. PMC: 2714480. DOI: 10.1158/1078-0432.CCR-08-1813. View

Deming D, Ninan J, Bailey H, Kolesar J, Eickhoff J, Reid J . A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors. Invest New Drugs. 2013; 32(2):323-9. PMC: 3949160. DOI: 10.1007/s10637-013-0035-8. View

Mann B, Johnson J, He K, Sridhara R, Abraham S, Booth B . Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma. Clin Cancer Res. 2007; 13(8):2318-22. DOI: 10.1158/1078-0432.CCR-06-2672. View

Pellom Jr S, Shanker A . Development of Proteasome Inhibitors as Therapeutic Drugs. J Clin Cell Immunol. 2013; S5:5. PMC: 3546515. DOI: 10.4172/2155-9899.s5-005. View

Fuino L, Bali P, Wittmann S, Donapaty S, Guo F, Yamaguchi H . Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther. 2003; 2(10):971-84. View

Mitsiades N, Mitsiades C, Poulaki V, Chauhan D, Fanourakis G, Gu X . Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci U S A. 2002; 99(22):14374-9. PMC: 137891. DOI: 10.1073/pnas.202445099. View

10.

Schelman W, Traynor A, Holen K, Kolesar J, Attia S, Hoang T . A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies. Invest New Drugs. 2013; 31(6):1539-46. PMC: 3901262. DOI: 10.1007/s10637-013-0029-6. View

11.

Brehm A, Nielsen S, Miska E, McCance D, Reid J, Bannister A . The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J. 1999; 18(9):2449-58. PMC: 1171327. DOI: 10.1093/emboj/18.9.2449. View

12.

Dimopoulos M, Siegel D, Lonial S, Qi J, Hajek R, Facon T . Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013; 14(11):1129-1140. DOI: 10.1016/S1470-2045(13)70398-X. View

13.

Marks P, Dokmanovic M . Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs. 2005; 14(12):1497-511. DOI: 10.1517/13543784.14.12.1497. View

14.

Lin K, Guarnieri F, Staveley-OCarroll K, Levitsky H, August J, Pardoll D . Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 1996; 56(1):21-6. View

15.

Hoang T, Campbell T, Zhang C, Kim K, Kolesar J, Oettel K . Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study. Invest New Drugs. 2013; 32(1):195-9. PMC: 4310688. DOI: 10.1007/s10637-013-9980-5. View

16.

Zhang Q, Wang L, Zhang Y, Jiang X, Yang F, Wu W . The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis. Leukemia. 2009; 23(8):1507-14. DOI: 10.1038/leu.2009.41. View

17.

Muscal J, Thompson P, Horton T, Ingle A, Ahern C, McGovern R . A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: a Children's Oncology Group phase I consortium study (ADVL0916). Pediatr Blood Cancer. 2012; 60(3):390-5. PMC: 3511610. DOI: 10.1002/pbc.24271. View

18.

Bolden J, Peart M, Johnstone R . Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006; 5(9):769-84. DOI: 10.1038/nrd2133. View

19.

Kim D, Hung C, Wu T . Monitoring the trafficking of adoptively transferred antigen- specific CD8-positive T cells in vivo, using noninvasive luminescence imaging. Hum Gene Ther. 2007; 18(7):575-88. DOI: 10.1089/hum.2007.038. View

20.

Sato A, Asano T, Ito K, Asano T . Vorinostat and bortezomib synergistically cause ubiquitinated protein accumulation in prostate cancer cells. J Urol. 2012; 188(6):2410-8. DOI: 10.1016/j.juro.2012.07.108. View