A novel synergistic therapeutic strategy for colorectal cancer with microsatellite stability
作者单位：National Key Laboratory of Medical Immunology & Institute of ImmunologyNavy Military Medical University
会议名称：《第十三届全国免疫学学术大会》
会议日期：2018年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：colorectal cancer decitabine microsatellite stability T cell receptor tumor immunotherapy
摘 要：Colorectal cancer(CRC) with microsatellite instability-high(MSI-H) has good clinical response in PD-1/PD-L1 blockades immunotherapy. However, the therapeutic efficacy for microsatellite instability-low(MSI-L) and microsatellite stable(MSS) patients needs further improvement. In our previous study, we have demonstrated that low dose Decitabine(5-aza-2’-deoxynucleoside, DAC) as a demethylation drug, could increase the immunogenicity of tumor cells and then recruit more lymphocytes to the tumor tissue, which provided a good tumor microenvironment for the PD-1 *** also found that tumor associated antigens including NY-ESO-1 could be induced or up-regulated by low dose DAC via demethylation of promoter region, which provides targets for immunotherapy. Antigen specific T cell receptor engineered T cells(TCR-T) are potential for solid tumors and attracting more and more attention. Here we prepared the NYESO-1 specific TCR-T cells by lentivirus transfection that recognized the NY-ESO-1157-165 epitope SLLMWITQC of HLA-A2 restricted, and confirmed the specific recognition and anti-tumor effect on T2 cells loaded with cognate peptides and different tumor cell lines with different phenotypes of HLA-A2 and NY-ESO-1 in vitro. Then, we also found that the TCR-T cells could recognize the NY-ESO-1 induced by DAC and showed cytotoxicity on DAC-treated MSS CRC cells in vitro and in immune-deficient mice model. So, we provided with a synergistic therapeutic strategy of the combination DAC and TCR-T cells for CRC with MSS, which may also be effective in other epithelial malignancies.