Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nürnberg, Universitätsstrasse 27, Erlangen, Germany.
Radiother Oncol. 2012 Jul;104(1):131-8. doi: 10.1016/j.radonc.2012.05.003. Epub 2012 Jun 9.
Dendritic cells (DCs) and regulatory T cells (Treg) play a major role in anti-tumor immune response of cancer patients. We investigated the effect of radiochemotherapy on patients' blood immune cells and their predictive value for tumor response.
DCs and Treg of colorectal cancer (CRC) or breast cancer (BC) patients were examined through multicolor flow cytometry before the beginning and after the first week of radiochemotherapy (RCT). DCs were stained for BDCA1 and BDCA2, Treg were stained for CD4, CD25, CD127 and FoxP3. IL-2, IL-10 and TNF-α plasma levels of CRC patients were also determined. We examined the interrelationship between immune cell count alterations, applied dose values, cytokine plasma levels as well as histopathological parameters.
DCs were increased in BC and CRC patients compared to healthy control individuals (HC). CRC patients had higher levels of Treg (59.0%) compared to BC patients (31.3%) and HC (27.0%). Treg of CRC (58.7% vs. 41.3% p<0.001) but not BC patients (31.3% vs. 38.8%, p=0.164) decreased distinctly after the first week of radiation therapy. Applied dose values and decrease of Treg correlated positively (r=0.216, p=0.054). We also found a positive correlation of IL-10 plasma levels and Treg levels (r=0.748, p=0.021). CRC patients with favorable tumor stage (<ypT3a) have higher levels of Treg after 5 days of RCT (49.4% vs. 34.0%, p=0.043).
Higher Treg levels are associated with favorable tumor stage. We hypothesize that a dramatic decrease of Treg after in vivo irradiation may be a good indicator for necessary dose adjustments in radiation therapy of CRC patients.
树突状细胞(DC)和调节性 T 细胞(Treg)在癌症患者的抗肿瘤免疫反应中发挥重要作用。我们研究了放化疗对患者血液免疫细胞的影响及其对肿瘤反应的预测价值。
通过多色流式细胞术,在放化疗(RCT)开始前和第一周后,检测结直肠癌(CRC)或乳腺癌(BC)患者的 DC 和 Treg。DC 用 BDCA1 和 BDCA2 染色,Treg 用 CD4、CD25、CD127 和 FoxP3 染色。还测定了 CRC 患者的 IL-2、IL-10 和 TNF-α 血浆水平。我们研究了免疫细胞计数改变、应用剂量值、细胞因子血浆水平以及组织病理学参数之间的相互关系。
与健康对照个体(HC)相比,BC 和 CRC 患者的 DC 增加。CRC 患者的 Treg 水平(59.0%)高于 BC 患者(31.3%)和 HC(27.0%)。CRC 患者的 Treg(58.7%对 41.3%,p<0.001),但不是 BC 患者(31.3%对 38.8%,p=0.164),在放射治疗第一周后明显下降。应用剂量值与 Treg 减少呈正相关(r=0.216,p=0.054)。我们还发现 IL-10 血浆水平与 Treg 水平之间存在正相关(r=0.748,p=0.021)。RCT 后 5 天,具有良好肿瘤分期(<ypT3a)的 CRC 患者的 Treg 水平较高(49.4%对 34.0%,p=0.043)。
较高的 Treg 水平与良好的肿瘤分期相关。我们假设,体内照射后 Treg 的急剧减少可能是 CRC 患者放射治疗中必要剂量调整的良好指标。