在非小细胞肺癌肺转移患者中，CD8+CD28+T 细胞增加可独立预测立体定向消融放疗的早期反应更好。
Increased CD8+CD28+ T cells independently predict better early response to stereotactic ablative radiotherapy in patients with lung metastases from non-small cell lung cancer.
机构信息
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
出版信息
J Transl Med. 2019 Apr 11;17(1):120. doi: 10.1186/s12967-019-1872-9.
BACKGROUND
Stereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells for tumor response after SABR are unknown. To that effect, we investigated the ability of pre-SABR immune cells in peripheral blood to predict early tumor response to SABR in patients with lung metastases from NSCLC.
METHODS
This study included 70 patients with lung metastases from NSCLC who were undergoing SABR. We evaluated the early tumor response 1 month and 6 months after SABR in these patients following RECIST 1.1 guidelines. Pre-SABR peripheral CD8+ T cell count, CD8+CD28+ T-cell count, CD8+CD28- T-cell count, CD4+ T-cell count, and Treg-cell count were measured using flow cytometry.
RESULTS
Increased CD8+CD28+ T-cell counts (14.43 ± 0.65 vs. 10.21 ± 0.66; P = 0.001) and CD4/Treg ratio (16.96 ± 1.76 vs. 11.91 ± 0.74; P = 0.011) were noted in 1-month responsive patients, compared with non-responsive patients. In univariate logistic analyses, high CD8+CD28+ T-cell counts (OR 0.12, 95% CI 0.03-0.48; P = 0.003), CD4/Treg ratio (OR 0.24, 95% CI 0.06-0.90; P = 0.035), and BED (OR 0.91, 95% CI 0.84-0.99; P = 0.032) predicted a 1-month tumor response to SABR. According to multivariate logistic analyses, the CD8+CD28+ T-cell count predicted a 1-month tumor response to SABR (OR 0.19, 95% CI 0.04-0.90; P = 0.037) independently. Furthermore, we confirmed the independent predictive value of the CD8+CD28+ T-cell count in predicting tumor response to SABR in 41 patients 6 months after treatment (OR 0.08, 95% CI 0.01-0.85; P = 0.039).
CONCLUSIONS
A pre-SABR CD8+CD28+ T-cell count could predict early tumor response to SABR in patients with lung metastases from NSCLC. Larger, independently prospective analyses are warranted to verify our findings.
背景
立体定向消融放疗（SABR）对非小细胞肺癌（NSCLC）转移灶具有显著的局部控制作用，部分原因是宿主的免疫状态。然而，SABR 后预测肿瘤反应的免疫细胞标志物尚不清楚。为此，我们研究了 NSCLC 肺转移患者 SABR 前外周血免疫细胞对 SABR 早期肿瘤反应的预测能力。
方法
本研究纳入了 70 例接受 SABR 的 NSCLC 肺转移患者。根据 RECIST 1.1 标准，我们评估了这些患者 SABR 后 1 个月和 6 个月的早期肿瘤反应。采用流式细胞术检测 SABR 前外周血 CD8+T 细胞计数、CD8+CD28+T 细胞计数、CD8+CD28-T 细胞计数、CD4+T 细胞计数和 Treg 细胞计数。
结果
与无反应患者相比，1 个月时应答患者的 CD8+CD28+T 细胞计数（14.43±0.65 与 10.21±0.66；P=0.001）和 CD4/Treg 比值（16.96±1.76 与 11.91±0.74；P=0.011）更高。单因素 logistic 分析显示，高 CD8+CD28+T 细胞计数（OR 0.12，95%CI 0.03-0.48；P=0.003）、CD4/Treg 比值（OR 0.24，95%CI 0.06-0.90；P=0.035）和生物有效剂量（OR 0.91，95%CI 0.84-0.99；P=0.032）预测 1 个月时 SABR 的肿瘤反应。根据多因素 logistic 分析，CD8+CD28+T 细胞计数可独立预测 1 个月时的肿瘤 SABR 反应（OR 0.19，95%CI 0.04-0.90；P=0.037）。此外，我们在 41 例治疗 6 个月后的患者中进一步证实了 CD8+CD28+T 细胞计数对 SABR 肿瘤反应的独立预测价值（OR 0.08，95%CI 0.01-0.85；P=0.039）。
结论
SABR 前 CD8+CD28+T 细胞计数可预测 NSCLC 肺转移患者 SABR 的早期肿瘤反应。需要更大规模、独立的前瞻性分析来验证我们的研究结果。
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