Tumour Immunology Group, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia.
Br J Cancer. 2012 Sep 25;107(7):1107-15. doi: 10.1038/bjc.2012.362. Epub 2012 Aug 21.
There is increasing interest in combining chemotherapy with immunotherapy. However, the effects of chemotherapy on the human immune system are largely unknown.
Longitudinal changes in peripheral T-cell subsets in 40 patients with malignant mesothelioma (MM) or advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy were assessed by flow cytometry and evaluated for associations with clinical outcome.
Proliferating T cells of all subsets were almost entirely depleted at day 8 following chemotherapy, but rapidly recovered above baseline levels. Regulatory T cells (Treg) were most profoundly depleted at this time point. A greater increase in CD8(+) T-cell proliferation following one treatment cycle was associated with improved overall survival in univariate (hazard ratio (HR)=0.40; P<0.05) and multivariate (HR=0.17; P<0.01) analyses. A greater increase in the ratio of CD8(+) T cell to Treg proliferation was also predictive of better prognosis.
Chemotherapy potentially provides a favourable environment for the development of anti-tumour immunity through transient Treg depletion and regeneration of the T-cell pool. Change in CD8(+) T-cell proliferation after one cycle of chemotherapy may represent a useful prognostic indicator in patients with MM and NSCLC.
联合化疗和免疫疗法的兴趣日益增加。然而,化疗对人体免疫系统的影响在很大程度上是未知的。
通过流式细胞术评估 40 例患有恶性间皮瘤(MM)或晚期非小细胞肺癌(NSCLC)的患者在接受铂类化疗后外周 T 细胞亚群的纵向变化,并评估其与临床结果的相关性。
化疗后第 8 天,所有亚群的增殖性 T 细胞几乎完全耗尽,但迅速恢复到基线以上水平。此时 Treg 细胞被最严重地耗尽。一个治疗周期后 CD8(+) T 细胞增殖增加更多与单变量(风险比(HR)=0.40;P<0.05)和多变量(HR=0.17;P<0.01)分析中的总生存期改善相关。CD8(+) T 细胞与 Treg 增殖比率的增加也预示着更好的预后。
化疗通过短暂的 Treg 耗竭和 T 细胞池的再生,为抗肿瘤免疫的发展提供了有利的环境。化疗一个周期后 CD8(+) T 细胞增殖的变化可能是 MM 和 NSCLC 患者的一个有用的预后指标。