RT Journal Article
SR Electronic
T1 The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 682617
DO 10.1101/682617
A1 Zhaoduan Liang
A1 Lili Qin
A1 Lei Chen
A1 Wenhui Li
A1 Chao Chen
A1 Yaling Huang
A1 Le Zhang
A1 Songming Liu
A1 Si Qiu
A1 Yuping Ge
A1 Wenting Peng
A1 Xinxin Lin
A1 Xuan Dong
A1 Xiuqing Zhang
A1 Bo Li
YR 2019
UL http://biorxiv.org/content/early/2019/07/03/682617.abstract
AB Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-γ. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.AbbreviationsCRCcolorectal cancerMMRdeficient mismatch repairMSI-Hhighly microsatellite instablepMMRproficient mismatch repairMSSmicrosatellite stableADCautologous tumor lysate DCCARchimeric antigen receptorTAAtumor associated antigenCEAcarcinoembryonic antigenHER2human epidermal growth factor receptor-2TSAtumor-specific antigenMHCmajor histocompatibility complexTMBtumor mutational burdenTCRT-cell receptorPRMparallel reaction monitoringTILtumor infiltrating lymphocyteMSmass spectrometryATCCAmerican Type Culture CollectionPBMCperipheral blood mononuclear cellICGCInternational Cancer Genome ConsortiumCOCA-CNChina-Colorectal Cancer ProjectInDelinsertions or deletionEPICEpitope Presentation Integrated predictionMITDMHC class I trafficking signalCTLcytotoxic lymphocyteELISPOTenzyme-linked immunospotFACSfluorescence-activated cell sortingGEMGel Bead in Emulsion