TY - JOUR
T1 - RNA editing derived epitopes function as cancer antigens to elicit immune responses
AU - Zhang, Minying
AU - Fritsche, Jens
AU - Roszik, Jason
AU - Williams, Leila J.
AU - Peng, Xinxin
AU - Chiu, Yulun
AU - Tsou, Chih Chiang
AU - Hoffgaard, Franziska
AU - Goldfinger, Valentina
AU - Schoor, Oliver
AU - Talukder, Amjad
AU - Forget, Marie A.
AU - Haymaker, Cara
AU - Bernatchez, Chantale
AU - Han, Leng
AU - Tsang, Yiu Huen
AU - Kong, Kathleen
AU - Xu, Xiaoyan
AU - Scott, Kenneth L.
AU - Singh-Jasuja, Harpreet
AU - Lizee, Greg
AU - Liang, Han
AU - Weinschenk, Toni
AU - Mills, Gordon B.
AU - Hwu, Patrick
N1 - Funding Information:
This work was supported by the following grants and foundations: Philanthropic contribution to University of Texas MD Anderson MoonShot-Talla for melanoma and EI Paso foundation (P.H.). Cancer Prevention Research Institute of Texas foundation (Immatics, DP150029). NIH R01 CA175486 (H.L.), U24CA209851 (H.L. and G.B.M.). CPRIT RP130397 (Y.C.). Philanthropic Bob Ladd funds (M.Z). Thanks to all members in Clinical TIL Production center of Department of Melanoma Medical Oncology MD Anderson Cancer Center for making TILs and tumour cell lines. Thanks to the bio-banking team at Immatics for sample acquisition, the Discovery lab team for preparation of tissues, DNA, RNA and peptides, the mass spec team for peptide analysis and validation, the CMC team for peptide synthesis and the bioinformatics team for data analysis. Thanks to Cassian Yee and the Lab members for providing the protocol and sharing their method of isolating and growing specific T cells from PBMCs.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
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.
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U2 - 10.1038/s41467-018-06405-9
DO - 10.1038/s41467-018-06405-9
M3 - Article
C2 - 30254248
AN - SCOPUS:85053819484
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3919
ER -