PT - JOURNAL ARTICLE AU - Zhaoduan Liang AU - Lili Qin AU - Lei Chen AU - Wenhui Li AU - Chao Chen AU - Yaling Huang AU - Le Zhang AU - Songming Liu AU - Si Qiu AU - Yuping Ge AU - Wenting Peng AU - Xinxin Lin AU - Xuan Dong AU - Xiuqing Zhang AU - Bo Li TI - The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic AID - 10.1101/682617 DP - 2019 Jan 01 TA - bioRxiv PG - 682617 4099 - http://biorxiv.org/content/early/2019/07/03/682617.short 4100 - http://biorxiv.org/content/early/2019/07/03/682617.full 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