Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

被引：185

作者：

Al Emran, Abdullah ^{[1
]}

Chatterjee, Aniruddha ^{[2
,3
]}

Rodger, Euan J. ^{[2
,3
]}

Tiffen, Jessamy C. ^{[1
]}

Gallagher, Stuart J. ^{[1
]}

Eccles, Michael R. ^{[2
,3
]}

Hersey, Peter ^{[1
]}

机构：

[1] Univ Sydney, Royal Prince Alfred Hosp, Centenary Inst, Melanoma Immunol & Oncol Grp, Camperdown, NSW 2050, Australia

[2] Univ Otago, Dunedin Sch Med, Dept Pathol, 270 Great King St, Dunedin 9054, New Zealand

[3] Maurice Wilkins Ctr Mol Biodiscovery, Level,3A Symonds St, Auckland, New Zealand

来源：

TRENDS IN IMMUNOLOGY | 2019年 / 40卷 / 04期

基金：

英国医学研究理事会;

关键词：

CD8; T-CELLS; SILENCED GENES; STAGE-III; CANCER; EXPRESSION; PD-1; INHIBITOR; CHROMATIN; DIFFERENTIATION; PATHWAYS;

D O I：

10.1016/j.it.2019.02.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Methylation of DNA at CpG sites is the most common and stable of epigenetic changes in cancer. Hypermethylation acts to limit immune checkpoint blockade immunotherapy by inhibiting endogenous interferon responses needed for recognition of cancer cells. By contrast, global hypomethylation results in the expression of programmed death ligand 1 (PD-L1) and inhibitory cytokines, accompanied by epithelial-mesenchymal changes that can contribute to immunosuppression. The drivers of these contrasting methylation states are not well understood. DNA methylation also plays a key role in cytotoxic T cell 'exhaustion' associated with tumor progression. We present an updated exploratory analysis of how DNA methylation may define patient subgroups and can be targeted to develop tailored treatment combinations to help improve patient outcomes.

引用

页码：328 / 344

页数：17

共 116 条

[91]

PD-1 blockade induces responses by inhibiting adaptive immune resistance [J].

Tumeh, Paul C. ;

Harview, Christina L. ;

Yearley, Jennifer H. ;

Shintaku, I. Peter ;

Taylor, Emma J. M. ;

Robert, Lidia ;

Chmielowski, Bartosz ;

Spasic, Marko ;

Henry, Gina ;

Ciobanu, Voicu ;

West, Alisha N. ;

Carmona, Manuel ;

Kivork, Christine ;

Seja, Elizabeth ;

Cherry, Grace ;

Gutierrez, Antonio J. ;

Grogan, Tristan R. ;

Mateus, Christine ;

Tomasic, Gorana ;

Glaspy, John A. ;

Emerson, Ryan O. ;

Robins, Harlan ;

Pierce, Robert H. ;

Elashoff, David A. ;

Robert, Caroline ;

Ribas, Antoni .

NATURE, 2014, 515 (7528) :568-+

[92]

The Polycomb Protein Ezh2 Regulates Differentiation and Plasticity of CD4+ T Helper Type 1 and Type 2 Cells [J].

Tumes, Damon J. ;

Onodera, Atsushi ;

Suzuki, Akane ;

Shinoda, Kenta ;

Endo, Yusuke ;

Iwamura, Chiaki ;

Hosokawa, Hiroyuki ;

Koseki, Haruhiko ;

Tokoyoda, Koji ;

Suzuki, Yutaka ;

Motohashi, Shinichiro ;

Nakayama, Toshinori .

IMMUNITY, 2013, 39 (05) :819-832

[93]

Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance [J].

Vaughan, Robert M. ;

Dickson, Bradley M. ;

Cornett, Evan M. ;

Harrison, Joseph S. ;

Kuhlman, Brian ;

Rothbart, Scott B. .

NUCLEIC ACIDS RESEARCH, 2018, 46 (09) :4405-4416

[94]

The Polycomb group protein EZH2 directly controls DNA methylation [J].

Viré, E ;

Brenner, C ;

Deplus, R ;

Blanchon, L ;

Fraga, M ;

Didelot, C ;

Morey, L ;

Van Eynde, A ;

Bernard, D ;

Vanderwinden, JM ;

Bollen, M ;

Esteller, M ;

Di Croce, L ;

de Launoit, Y ;

Fuks, F .

NATURE, 2006, 439 (7078) :871-874

[95]

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity [J].

Wang, David ;

Quiros, Jason ;

Mahuron, Kelly ;

Pai, Chien-Chun ;

Ranzani, Valeria ;

Young, Arabella ;

Silveria, Stephanie ;

Harwin, Tory ;

Abnousian, Arbi ;

Pagani, Massimiliano ;

Rosenblum, Michael D. ;

Van Gool, Frederic ;

Fong, Lawrence ;

Bluestone, Jeffrey A. ;

DuPage, Michel .

CELL REPORTS, 2018, 23 (11) :3262-3274

[96]

cGAS is essential for the antitumor effect of immune checkpoint blockade [J].

Wang, Hua ;

Hu, Shuiqing ;

Chen, Xiang ;

Shi, Heping ;

Chen, Chuo ;

Sun, Lijun ;

Chen, Zhijian J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (07) :1637-1642

[97]

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma [J].

Weber, J. ;

Mandala, M. ;

Del Vecchio, M. ;

Gogas, H. J. ;

Arance, A. M. ;

Cowey, C. L. ;

Dalle, S. ;

Schenker, M. ;

Chiarion-Sileni, V. ;

Marquez-Rodas, I. ;

Grob, J-J. ;

Butler, M. O. ;

Middleton, M. R. ;

Maio, M. ;

Atkinson, V. ;

Queirolo, P. ;

Gonzalez, R. ;

Kudchadkar, R. R. ;

Smylie, M. ;

Meyer, N. ;

Mortier, L. ;

Atkins, M. B. ;

Long, G. V. ;

Bhatia, S. ;

Lebbe, C. ;

Rutkowski, P. ;

Yokota, K. ;

Yamazaki, N. ;

Kim, T. M. ;

de Pril, V. ;

Sabater, J. ;

Qureshi, A. ;

Larkin, J. ;

Ascierto, P. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (19) :1824-1835

[98]

Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression [J].

Westerlund, Isabelle ;

Shi, Yao ;

Toskas, Konstantinos ;

Fell, Stuart M. ;

Li, Shuijie ;

Surova, Olga ;

Sodersten, Erik ;

Kogner, Per ;

Nyman, Ulrika ;

Schlisio, Susanne ;

Holmberg, Johan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (30) :E6137-E6146

[99]

Molecular and cellular insights into T cell exhaustion [J].

Wherry, E. John ;

Kurachi, Makoto .

NATURE REVIEWS IMMUNOLOGY, 2015, 15 (08) :486-499

[100]

Final Results From a Multicenter, International, Pivotal Study of Romidepsin in Refractory Cutaneous T-Cell Lymphoma [J].

Whittaker, Sean J. ;

Demierre, Marie-France ;

Kim, Ellen J. ;

Rook, Alain H. ;

Lerner, Adam ;

Duvic, Madeleine ;

Scarisbrick, Julia ;

Reddy, Sunil ;

Robak, Tadeusz ;

Becker, Juergen C. ;

Samtsov, Alexey ;

McCulloch, William ;

Kim, Youn H. .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (29) :4485-4491

← 3 4 5 6 7 8 9 10 11 12 →