Translational control of tumor immune escape via the eIF4F-STAT1-PD-L1 axis in melanoma

被引：214

作者：

Cerezo, Michael ^{[1
,2
]}

Guemiri, Ramdane ^{[1
,2
,3
,4
,5
]}

Druillennec, Sabine ^{[5
,6
,7
]}

Girault, Isabelle ^{[1
,2
]}

Malka-Mahieu, Helene ^{[3
,4
,5
]}

Shen, Shensi ^{[1
,2
]}

Allard, Delphine ^{[1
,2
]}

Martineau, Sylvain ^{[3
,4
,5
]}

Welsch, Caroline ^{[1
,2
,3
,4
,5
]}

Agoussi, Sandrine ^{[1
,2
]}

Estrada, Charlene ^{[5
,6
,7
]}

Adam, Julien ^{[1
,8
]}

Libenciuc, Cristina ^{[9
]}

Routier, Emilie ^{[9
]}

Roy, Severine ^{[9
]}

Desaubry, Laurent ^{[10
]}

Eggermont, Alexander M. ^{[2
,9
]}

Sonenberg, Nahum ^{[11
]}

Scoazec, Jean Yves ^{[8
]}

Eychene, Alain ^{[5
,6
,7
]}

Vagner, Stephan ^{[3
,4
,5
,9
]}

Robert, Caroline ^{[1
,2
,9
]}

机构：

[1] INSERM, U981, Villejuif, France

[2] Univ Paris Saclay, Univ Paris Sud, Le Kremlin Bicetre, France

[3] PSL Res Univ, CNRS, UMR 3348, Inst Curie, Orsay, France

[4] Univ Paris Saclay, Univ Paris Sud, CNRS, UMR 3348, Orsay, France

[5] Equipe Labellisee Ligue Canc, Paris, France

[6] PSL Res Univ, CNRS, UMR 3347, Inst Curie,INSERM,U1021, Orsay, France

[7] Univ Paris Saclay, Univ Paris Sud, CNRS, INSERM,U1021,UMR 3347, Orsay, France

[8] Gustave Roussy Univ Paris Saclay, Dept Pathol & Lab Med BIOpath, Villejuif, France

[9] Gustave Roussy Univ Paris Saclay, Oncol Dept, Villejuif, France

[10] Strasbourg Univ, CNRS, UMR7200, Illkirch Graffenstaden, France

[11] McGill Univ, Dept Biochem, Montreal, PQ, Canada

来源：

NATURE MEDICINE | 2018年 / 24卷 / 12期

关键词：

INITIATION COMPLEX; ONCOGENIC RAS; RNA HELICASE; MICE LACKING; RESISTANCE; EIF4F; PD-L1; INHIBITOR; BRAF; SENSITIVITY;

D O I：

10.1038/s41591-018-0217-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Preventing the immune escape of tumor cells by blocking inhibitory checkpoints, such as the interaction between programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) receptor, is a powerful anticancer approach. However, many patients do not respond to checkpoint blockade. Tumor PD-L1 expression is a potential efficacy biomarker, but the complex mechanisms underlying its regulation are not completely understood. Here, we show that the eukaryotic translation initiation complex, eIF4F, which binds the 5' cap of mRNAs, regulates the surface expression of interferon-gamma-induced PD-L1 on cancer cells by regulating translation of the mRNA encoding the signal transducer and activator of transcription 1 (STAT1) transcription factor. eIF4F complex formation correlates with response to immunotherapy in human melanoma. Pharmacological inhibition of eIF4A, the RNA helicase component of eIF4F, elicits powerful antitumor immune-mediated effects via PD-L1 downregulation. Thus, eIF4A inhibitors, in development as anticancer drugs, may also act as cancer immunotherapies.

引用

页码：1877 / +

页数：13

共 58 条

[1]

The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus [J].

Banko, JL ;

Poulin, F ;

Hou, LF ;

DeMaria, CT ;

Sonenberg, N ;

Klann, E .

JOURNAL OF NEUROSCIENCE, 2005, 25 (42) :9581-9590

[2]

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

[3]

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Xu, Bihui ;

Qiu, Yu ;

Wu, Tony J. ;

Dada, Hannah ;

Twyman-Saint Victor, Christina ;

Cucolo, Lisa ;

Lee, David S. M. ;

Pauken, Kristen E. ;

Huang, Alexander C. ;

Gangadhar, Tara C. ;

Amaravadi, Ravi K. ;

Schuchter, Lynn M. ;

Feldman, Michael D. ;

Ishwaran, Hemant ;

Vonderheide, Robert H. ;

Maity, Amit ;

Wherry, E. John ;

Minn, Andy J. .

CELL, 2016, 167 (06) :1540-+

[4]

Targeting the translation machinery in cancer [J].

Bhat, Mamatha ;

Robichaud, Nathaniel ;

Hulea, Laura ;

Sonenberg, Nahum ;

Pelletier, Jerry ;

Topisirovic, Ivan .

NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (04) :261-278

[5]

Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model [J].

Bordeleau, Marie-Eve ;

Robert, Francis ;

Gerard, Baudouin ;

Lindqvist, Lisa ;

Chen, Samuel M. H. ;

Wendel, Hans-Guido ;

Brem, Brigitte ;

Greger, Harald ;

Lowe, Scott W. ;

Porco, John A., Jr. ;

Pelletier, Jerry .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2651-2660

[6]

Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A [J].

Bordeleau, ME ;

Mori, A ;

Oberer, M ;

Lindqvist, L ;

Chard, LS ;

Higa, T ;

Belsham, GJ ;

Wagner, G ;

Tanaka, J ;

Pelletier, J .

NATURE CHEMICAL BIOLOGY, 2006, 2 (04) :213-220

[7]

Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation [J].

Bordeleau, ME ;

Matthews, J ;

Wojnar, JM ;

Lindqvist, L ;

Novac, O ;

Jankowsky, E ;

Sonenberg, N ;

Northcote, P ;

Teesdale-Spittlet, P ;

Pelletier, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (30) :10460-10465

[8]

In Vitro and In Vivo Anti-Melanoma Effects of Ciglitazone [J].

Botton, Thomas ;

Puissant, Alexandre ;

Bahadoran, Philippe ;

Annicotte, Jean-Sebastien ;

Fajas, Lluis ;

Ortonne, J-P ;

Gozzerino, Genevieve ;

Zamoum, Thamilla ;

Tartare-Deckert, Sophie ;

Bertolotto, Corine ;

Ballotti, Robert ;

Rocchi, Stephane .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (05) :1208-1218

[9]

eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies [J].

Boussemart, Lise ;

Malka-Mahieu, Helene ;

Girault, Isabelle ;

Allard, Delphine ;

Hemmingsson, Oskar ;

Tomasic, Gorana ;

Thomas, Marina ;

Basmadjian, Christine ;

Ribeiro, Nigel ;

Thuaud, Frederic ;

Mateus, Christina ;

Routier, Emilie ;

Kamsu-Kom, Nyam ;

Agoussi, Sandrine ;

Eggermont, Alexander M. ;

Desaubry, Laurent ;

Robert, Caroline ;

Vagner, Stephan .

NATURE, 2014, 513 (7516) :105-+

[10]

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity [J].

Burr, Marian L. ;

Sparbier, Christina E. ;

Chan, Yih-Chih ;

Williamson, James C. ;

Woods, Katherine ;

Beavis, Paul A. ;

Lam, Enid Y. N. ;

Henderson, Melissa A. ;

Bell, Charles C. ;

Stolzenburg, Sabine ;

Gilan, Omer ;

Bloor, Stuart ;

Noori, Tahereh ;

Morgens, David W. ;

Bassik, Michael C. ;

Neeson, Paul J. ;

Behren, Andreas ;

Darcy, Phillip K. ;

Dawson, Sarah-Jane ;

Voskoboinik, Ilia ;

Trapani, Joseph A. ;

Cebon, Jonathan ;

Lehner, Paul J. ;

Dawson, Mark A. .

NATURE, 2017, 549 (7670) :101-105

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