PMID- 30254248 OWN - NLM STAT- MEDLINE DCOM- 20190114 LR - 20190925 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Sep 25 TI - RNA editing derived epitopes function as cancer antigens to elicit immune responses. PG - 3919 LID - 10.1038/s41467-018-06405-9 [doi] LID - 3919 AB - In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editing are indeed naturally presented by human leukocyte antigen (HLA) molecules. We provide evidence that effector CD8(+) T cells specific for edited peptides derived from cyclin I are present in human tumours and attack tumour cells that are presenting these epitopes. We show that subpopulations of cancer patients have increased peptide levels and that levels of edited RNA correlate with peptide copy numbers. These findings demonstrate that RNA editing extends the classes of HLA presented self-antigens and that these antigens can be recognised by the immune system. FAU - Zhang, Minying AU - Zhang M AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Fritsche, Jens AU - Fritsche J AUID- ORCID: 0000-0002-5557-8577 AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. FAU - Roszik, Jason AU - Roszik J AUID- ORCID: 0000-0002-4561-6170 AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Williams, Leila J AU - Williams LJ AUID- ORCID: 0000-0002-9833-859X AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Peng, Xinxin AU - Peng X AD - Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, TX, 77230, USA. FAU - Chiu, Yulun AU - Chiu Y AD - Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, TX, 77230, USA. FAU - Tsou, Chih-Chiang AU - Tsou CC AD - Immatics US, 2130W Holcombe Blvd, Houston, TX, 77030, USA. FAU - Hoffgaard, Franziska AU - Hoffgaard F AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. FAU - Goldfinger, Valentina AU - Goldfinger V AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. FAU - Schoor, Oliver AU - Schoor O AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. FAU - Talukder, Amjad AU - Talukder A AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Forget, Marie A AU - Forget MA AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Haymaker, Cara AU - Haymaker C AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Bernatchez, Chantale AU - Bernatchez C AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Han, Leng AU - Han L AUID- ORCID: 0000-0002-7380-2640 AD - Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, 6431 Fannin Street MSB 6.200, Houston, TX, 77030, USA. FAU - Tsang, Yiu-Huen AU - Tsang YH AD - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, BCM225, Houston, TX, 77030, USA. FAU - Kong, Kathleen AU - Kong K AD - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, BCM225, Houston, TX, 77030, USA. FAU - Xu, Xiaoyan AU - Xu X AD - Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, TX, 77230, USA. AD - Department of Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, 77 Puhe Rd, Shenbei Xinqu, Shenyang Shi, 110122, China. FAU - Scott, Kenneth L AU - Scott KL AD - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, BCM225, Houston, TX, 77030, USA. FAU - Singh-Jasuja, Harpreet AU - Singh-Jasuja H AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. AD - Immatics US, 2130W Holcombe Blvd, Houston, TX, 77030, USA. FAU - Lizee, Greg AU - Lizee G AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. FAU - Liang, Han AU - Liang H AUID- ORCID: 0000-0001-7633-286X AD - Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, P. O. Box 301402, Houston, TX, 77230, USA. AD - Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77230, USA. FAU - Weinschenk, Toni AU - Weinschenk T AUID- ORCID: 0000-0001-8644-0290 AD - Immatics Biotechnologies, Paul-Ehrlich-Str 15, 72076, Tubingen, Germany. weinschenk@immatics.com. AD - Immatics US, 2130W Holcombe Blvd, Houston, TX, 77030, USA. weinschenk@immatics.com. FAU - Mills, Gordon B AU - Mills GB AD - Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77230, USA. gmills@mdanderson.org. FAU - Hwu, Patrick AU - Hwu P AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Unit 904, Houston, TX, 77054, USA. phwu@mdanderson.org. LA - eng GR - R01 CA175486/CA/NCI NIH HHS/United States GR - U01 CA217842/CA/NCI NIH HHS/United States GR - U24 CA209851/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180925 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Antigens, Neoplasm) RN - 0 (Cyclin I) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (Peptides) SB - IM MH - Antigen Presentation/immunology MH - Antigens, Neoplasm/*immunology MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cell Line, Tumor MH - Cells, Cultured MH - Cyclin I/genetics/immunology/metabolism MH - Cytotoxicity, Immunologic/immunology MH - Epitopes/*immunology MH - HLA Antigens/immunology MH - Humans MH - Immune System/*immunology MH - Neoplasms/genetics/*immunology/metabolism MH - Peptides/genetics/immunology/metabolism MH - Proteogenomics/methods MH - RNA Editing/*immunology PMC - PMC6156571 COIS- J.F., F.H., V.G., O.S., H.S.-J., C.-C.T. and T.W. are employees of Immatics. H.S.-J. and T.W. are shareholder of Immatics Biotechnologies. H.L. is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. P.H. is a Scientific Advisor for Immatics. The remaining authors declare no competing interests. EDAT- 2018/09/27 06:00 MHDA- 2019/01/15 06:00 PMCR- 2018/09/25 CRDT- 2018/09/27 06:00 PHST- 2018/05/22 00:00 [received] PHST- 2018/07/30 00:00 [accepted] PHST- 2018/09/27 06:00 [entrez] PHST- 2018/09/27 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/09/25 00:00 [pmc-release] AID - 10.1038/s41467-018-06405-9 [pii] AID - 6405 [pii] AID - 10.1038/s41467-018-06405-9 [doi] PST - epublish SO - Nat Commun. 2018 Sep 25;9(1):3919. doi: 10.1038/s41467-018-06405-9.