γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
我们的发现表明,活化的γδ T细胞可能是SCLC治疗的有价值靶点。
英文原题:FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer.
FOXM1在多种癌症类型中高表达,被认为是癌症进展的关键驱动因素。
FOXM1在多种癌症类型中高表达,被认为是癌症进展的关键驱动因素。因此,我们评估了FOXM1的免疫原性,并探讨了利用T细胞受体(TCR)工程靶向该转录因子的可行性。我们鉴定出源自FOXM1的表位,这些表位在HLA-A*02:01、HLA-A*24:02和HLA-A*23:01上具有免疫原性,经内源性加工和呈递,并导致T细胞活化和细胞毒性T细胞反应。在生成TCR-T细胞后,分别通过肽剂量反应和X-scan确认了敏感性和特异性。最重要的是,过继转移TCR工程T细胞导致肿瘤生长显著减少,并在荷瘤免疫缺陷小鼠模型中显著延长了生存期。我们的研究证实了FOXM1的免疫原性以及利用TCR工程靶向该抗原的可行性。
FOXM1 is highly expressed in various cancer types and considered a key driver of cancer progression. Accordingly, we evaluated the immunogenicity of FOXM1 and investigated the feasibility of targeting this transcription factor using T-cell receptor (TCR) engineering. We identified epitopes derived from FOXM1 which were immunogenic on HLA-A*02:01, HLA-A*24:02, and HLA-A*23:01, endogenously processed and presented, and resulted in T-cell activation and cytotoxic T-cell responses. Following the generation of TCR-T cells, sensitivity and specificity were confirmed by peptide dose-response and X-scan, respectively. Most importantly, adoptive transfer of TCR-engineered T cells led to a significant reduction in tumor growth, as well as significantly prolonged survival in a tumor-bearing immunocompromised murine model. Our studies confirm the immunogenicity of FOXM1 and feasibility of targeting this antigen using TCR engineering.
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