Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade

Nature

Volumn 565, Issue 7737, 2019, Pages 43-48

  Ishizuka, Jeffrey J ^a,b   Manguso, Robert T ^a,b   Cheruiyot, Collins K ^a,b   Bi, Kevin ^a,b   Panda, Arpit ^a,b,c   Iracheta Vellve, Arvin ^a,b   Miller, Brian C ^a,b   Du, Peter P ^a,b   Yates, Kathleen B ^a,b   Dubrot, Juan ^a,b   Buchumenski, Ilana ^d   Comstock, Dawn E ^a,b,c   Brown, Flavian D ^a,b,c   Ayer, Austin ^a,b   Kohnle, Ian C ^a,b   Pope, Hans W ^a,b   Zimmer, Margaret D ^a,b   Sen, Debattama R ^a,b,c   Lane Reticker, Sarah K ^a,b   Robitschek, Emily J ^a,b   Griffin, Gabriel K ^a,b,e   Collins, Natalie B ^a,b,f   Long, Adrienne H ^a,b   Doench, John G ^b   Kozono, David ^a   Levanon, Erez Y ^d   Haining, W Nicholas ^a,b,f   more..

^a DANA FARBER CANCER INSTITUTE   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d BAR ILAN UNIVERSITY   (Israel)

^e BRIGHAM AND WOMEN S HOSPITAL   (United States)

^f BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR VACCINE; PROGRAMMED DEATH 1 RECEPTOR ANTIBODY; UNCLASSIFIED DRUG; ADAR1 PROTEIN, HUMAN; ADENOSINE DEAMINASE; DOUBLE STRANDED RNA; G PROTEIN COUPLED RECEPTOR; HLA ANTIGEN CLASS 1; IFIH1 PROTEIN, MOUSE; INTERFERON; INTERFERON INDUCED HELICASE C DOMAIN CONTAINING PROTEIN 1; PDCD1 PROTEIN, HUMAN; PKR1 PROTEIN, MOUSE; PROGRAMMED DEATH 1 RECEPTOR; RNA BINDING PROTEIN;

ANTIGEN; CANCER; ENZYME ACTIVITY; GENE; GENE EXPRESSION; IMMUNE RESPONSE; INDUCED RESPONSE; INHIBITION; LIGAND; TUMOR;

ADAR1 GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTATION; ARTICLE; CANCER CELL; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DOUBLE STRANDED RNA BINDING DOMAIN; FEMALE; GENE FUNCTION; GENE LOSS; GROWTH INHIBITION; LOSS OF FUNCTION MUTATION; MOUSE; NEOPLASM; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; RNA EDITING; TUMOR CELL; TUMOR IMMUNITY; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL CYCLE CHECKPOINT; CRISPR CAS SYSTEM; DEFICIENCY; DRUG EFFECT; DRUG RESISTANCE; EXPERIMENTAL MELANOMA; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; INFLAMMATION; METABOLISM; PHENOTYPE; TUMOR CELL LINE;

ADENOSINE DEAMINASE; ANIMALS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CRISPR-CAS SYSTEMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HISTOCOMPATIBILITY ANTIGENS CLASS I; IMMUNOTHERAPY; INFLAMMATION; INTERFERON-INDUCED HELICASE, IFIH1; INTERFERONS; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; PHENOTYPE; PROGRAMMED CELL DEATH 1 RECEPTOR; RECEPTORS, G-PROTEIN-COUPLED; RNA EDITING; RNA, DOUBLE-STRANDED; RNA-BINDING PROTEINS;

EID: 85059501861     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/s41586-018-0768-9     Document Type: Article

References (39)

1. Zaretsky, J. M. et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375, 819–829 (2016).
2. Gao, J. et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167, 397–404 (2016).
3. Yoshihama, S. et al. NLRC5/MHC class I transactivator is a target for immune evasion in cancer. Proc. Natl Acad. Sci. USA 113, 5999–6004 (2016).
4. Sade-Feldman, M. et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat. Commun. 8, 1136 (2017).
5. Manguso, R. T. et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547, 413–418 (2017).
6. Mannion, N. M. et al. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Reports 9, 1482–1494 (2014).
7. Liddicoat, B. J., Chalk, A. M. & Walkley, C. R. ADAR1, inosine and the immune sensing system: distinguishing self from non-self. Wiley Interdiscip. Rev. RNA 7, 157–172 (2016).
8. Ahmad, S. et al. Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation. Cell 172, 797–810.e13 (2018).
9. Chung, H. et al. Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172, P811–P824 (2018).
10. Deng, L. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843–852 (2014).
11. + T cells. Cancer Immunol. Immunother. 63, 259–271 (2014).
12. Twyman-Saint Victor, C. et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520, 373–377 (2015).
13. Wenzel, J., Uerlich, M., Haller, O., Bieber, T. & Tueting, T. Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist imiquimod. J. Cutan. Pathol. 32, 257–262 (2005).
14. Sainathan, S. K. et al. Toll-like receptor-7 ligand Imiquimod induces type I interferon and antimicrobial peptides to ameliorate dextran sodium sulfate-induced acute colitis. Inflamm. Bowel Dis. 18, 955–967 (2012).
15. Cho, J. H. et al. The TLR7 agonist imiquimod induces anti-cancer effects via autophagic cell death and enhances anti-tumoral and systemic immunity during radiotherapy for melanoma. Oncotarget 8, 24932–24948 (2017).
16. Patterson, J. B. & Samuel, C. E. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol. Cell. Biol. 15, 5376–5388 (1995).
17. George, C. X. & Samuel, C. E. Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible. Proc. Natl Acad. Sci. USA 96, 4621–4626 (1999).
18. Heidegger, S. et al. The RIG-I agonist 3pRNA synergizes with checkpoint blockade in cancer immunotherapy. Blood 126, 3436 (2015).
19. Goel, S. et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature 548, 471–475 (2017).
20. Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162, 974–986 (2015).
21. Li, H. et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 5, 587–598 (2014).
22. Ribas, A. et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 170, 1109–1119 (2017).
23. Juneja, V. R. et al. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J. Exp. Med. 214, 895–904 (2017).
24. McGranahan, N. et al. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171, 1259–1271 (2017).
25. Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568–571 (2014).
26. Ngwa, W., Tsiamas, P., Zygmanski, P., Makrigiorgos, G. M. & Berbeco, R. I. A multipurpose quality assurance phantom for the small animal radiation research platform (SARRP). Phys. Med. Biol. 57, 2575–2586 (2012).
27. Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
28. Waltman, L. & van Eck, N. J. A smart local moving algorithm for large-scale modularity-based community detection. Eur. Phys. J. B 86, 471 (2013).
29. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
30. DeTomaso, D. & Yosef, N. FastProject: a tool for low-dimensional analysis of single-cell RNA-Seq data. BMC Bioinformatics 17, 315 (2016).
31. Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417–425 (2015).
32. Schmieder, R. & Edwards, R. Quality control and preprocessing of metagenomic datasets. Bioinformatics 27, 863–864 (2011).
33. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
34. Bazak, L. et al. A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Res. 24, 365–376 (2014).
35. Porath, H. T., Carmi, S. & Levanon, E. Y. A genome-wide map of hyper-edited RNA reveals numerous new sites. Nat. Commun. 5, 4726 (2014).
36. Yu, G., Wang, L.-G. & He, Q.-Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382–2383 (2015).
37. Paz-Yaacov, N. et al. Elevated RNA Editing activity is a major contributor to transcriptomic diversity in tumors. Cell Reports 13, 267–276 (2015).
38. Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453–457 (2015).
39. Yoshihara, K. et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 4, 2612 (2013).