PMID- 38093017
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240314
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 625
IP  - 7995
DP  - 2024 Jan
TI  - Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides.
PG  - 593-602
LID - 10.1038/s41586-023-06834-7 [doi]
AB  - Emerging data have shown that previously defined noncoding genomes might encode 
      peptides that bind human leukocyte antigen (HLA) as cryptic antigens to stimulate 
      adaptive immunity(1,2). However, the significance and mechanisms of action of 
      cryptic antigens in anti-tumour immunity remain unclear. Here mass spectrometry 
      of the HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human 
      breast cancer samples identified HLA-I-binding cryptic antigenic peptides that 
      were noncanonically translated by a tumour-specific circular RNA (circRNA): 
      circFAM53B. The cryptic peptides efficiently primed naive CD4(+) and CD8(+) 
      T cells in an antigen-specific manner and induced anti-tumour immunity. 
      Clinically, the expression of circFAM53B and its encoded peptides was associated 
      with substantial infiltration of antigen-specific CD8(+) T cells and better 
      survival in patients with breast cancer and patients with melanoma. 
      Mechanistically, circFAM53B-encoded peptides had strong binding affinity to both 
      HLA-I and HLA-II molecules. In vivo, administration of vaccines consisting of 
      tumour-specific circRNA or its encoded peptides in mice bearing breast cancer 
      tumours or melanoma induced enhanced infiltration of tumour-antigen-specific 
      cytotoxic T cells, which led to effective tumour control. Overall, our findings 
      reveal that noncanonical translation of circRNAs can drive efficient anti-tumour 
      immunity, which suggests that vaccination exploiting tumour-specific circRNAs may 
      serve as an immunotherapeutic strategy against malignant tumours.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Huang, Di
AU  - Huang D
AUID- ORCID: 0000-0001-7304-4889
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Zhu, Xiaofeng
AU  - Zhu X
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Ye, Shuying
AU  - Ye S
AUID- ORCID: 0000-0003-1142-5269
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Zhang, Jiahui
AU  - Zhang J
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Liao, Jianyou
AU  - Liao J
AD  - Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Zhang, Ning
AU  - Zhang N
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Zeng, Xin
AU  - Zeng X
AD  - Program of Molecular Medicine, Zhongshan School of Medicine, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Wang, Jiawen
AU  - Wang J
AUID- ORCID: 0000-0002-0304-1591
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Yang, Bing
AU  - Yang B
AUID- ORCID: 0000-0002-1424-1222
AD  - Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Zhang, Yin
AU  - Zhang Y
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
FAU - Lao, Liyan
AU  - Lao L
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Chen, Jianing
AU  - Chen J
AUID- ORCID: 0000-0002-2748-5197
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Xin, Min
AU  - Xin M
AUID- ORCID: 0009-0000-5599-2017
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Nie, Yan
AU  - Nie Y
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China.
FAU - Saw, Phei Er
AU  - Saw PE
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
FAU - Su, Shicheng
AU  - Su S
AUID- ORCID: 0000-0003-2280-3587
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 
      sushch@mail.sysu.edu.cn.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China. sushch@mail.sysu.edu.cn.
AD  - Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, 
      Guangzhou, China. sushch@mail.sysu.edu.cn.
AD  - Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-Sen 
      University, Guangzhou, China. sushch@mail.sysu.edu.cn.
AD  - Biotherapy Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China. sushch@mail.sysu.edu.cn.
FAU - Song, Erwei
AU  - Song E
AUID- ORCID: 0000-0002-5400-9049
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen 
      Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 
      songew@mail.sysu.edu.cn.
AD  - Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, China. songew@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231213
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 0 (RNA, Circular)
SB  - IM
CIN - Nat Rev Drug Discov. 2024 Feb;23(2):103. PMID: 38225388
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - Antigens, Neoplasm/immunology
MH  - *Breast Neoplasms/genetics/immunology/mortality/pathology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Mass Spectrometry
MH  - *Melanoma/genetics/immunology/mortality/pathology
MH  - *Peptides/genetics/immunology
MH  - *Protein Biosynthesis
MH  - Ribosome Profiling
MH  - *RNA, Circular/genetics/metabolism
MH  - Survival Analysis
EDAT- 2023/12/14 00:42
MHDA- 2024/01/19 06:42
CRDT- 2023/12/13 23:44
PHST- 2022/08/11 00:00 [received]
PHST- 2023/11/03 00:00 [accepted]
PHST- 2024/01/19 06:42 [medline]
PHST- 2023/12/14 00:42 [pubmed]
PHST- 2023/12/13 23:44 [entrez]
AID - 10.1038/s41586-023-06834-7 [pii]
AID - 10.1038/s41586-023-06834-7 [doi]
PST - ppublish
SO  - Nature. 2024 Jan;625(7995):593-602. doi: 10.1038/s41586-023-06834-7. Epub 2023 
      Dec 13.