CLIN CANCER RES:4-1BB激动剂增强胰腺癌CD8+肿瘤浸润淋巴细胞功能

2017-12-07 MedSci MedSci原创

胰腺导管腺癌(PDAC)患者预后极差,需要疗效更好的治疗方法。肿瘤浸润淋巴细胞(TIL)过继细胞疗法(ACT)在其他肿瘤中表现出了良好的治疗效果。如在转移性黑色素瘤中出现过50%的总反应率。T细胞功能与胰腺癌患者总生存正相关。CLIN CANCER RES近期发表了一篇文章,研究增强CD8+TIL细胞识别自体肿瘤抗原的能力。此外还研究了肿瘤微环境中CD8+TIL的亚型和T细胞受体情况。

胰腺导管腺癌(PDAC)患者预后极差,需要疗效更好的治疗方法。肿瘤浸润淋巴细胞(TIL)过继细胞疗法(ACT)在其他肿瘤中表现出了良好的治疗效果。如在转移性黑色素瘤中出现过50%的总反应率。T细胞功能与胰腺癌患者总生存正相关。CLIN CANCER RES近期发表了一篇文章,研究增强CD8+TIL细胞识别自体肿瘤抗原的能力。此外还研究了肿瘤微环境中CD8+TIL的亚型和T细胞受体情况。

作者使用激动性4-1BB单抗提供4-1BB共刺激信号,评估TIL生长、亚型、比例和抗肿瘤功能改变。研究结果表明,在激动性4-1BB单抗的辅助下,PDAC肿瘤分离出的CD8+肿瘤浸润淋巴细胞生长能力增强。扩增的肿瘤浸润淋巴细胞是活化型而非最终分化亚型。此外,4-1BB共刺激比IL2单独刺激能够扩增出更大比例的克隆性CD8+肿瘤浸润淋巴细胞。两种培养方式培养出的肿瘤浸润淋巴细胞均通过MCHⅠ类识别自体肿瘤抗原。

文章最后认为,利用抗4-1BB单抗共刺激可以产生更多数量的肿瘤活性T细胞,增强TIL治疗的有效性。该研究结果表明胰腺癌TIL过继细胞治疗是一种可行的治疗方法,应在需要更好的治疗方案的患者中进行进一步研究。

原始出处:
Donastas Sakellariou-Thompson,Marie-Andree Forget,et al.4-1BB Agonist Focuses CD8+ Tumor-Infiltrating T-Cell Growth into a Distinct Repertoire Capable of Tumor Recognition in Pancreatic Cancer.CLIN CANCER RES.December 2017 doi:10.1158/1078-0432.CCR-17-0831

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    2017-12-12 llaq

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    2017-12-07 sunfeifeiyang

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