Department of Urology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, 150 06 Prague, Czech Republic.
Immunol Lett. 2013 May;152(2):144-50. doi: 10.1016/j.imlet.2013.05.010. Epub 2013 May 27.
We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.
我们评估了 37 例新诊断的肾细胞癌(RCC)患者肿瘤和外周血(PB)中的树突状细胞(DC)、调节性 T 淋巴细胞(Treg)和中性粒细胞,并将这些参数与肿瘤分期(早期-T1、2,晚期-T3、4 和转移性疾病)相关联。RCC 患者血液中的髓样和浆细胞样 DC 数量高于健康对照组。与疾病分期无关,肿瘤中来自 CD45+细胞的髓样树突状细胞(mDC)的百分比高于外周血。这些细胞在外周的成熟标志物(表达 CD83 的细胞)的百分比在早期阶段更高。早期组 PB 中的浆细胞样树突状细胞(pDC)数量在早期和晚期组中相似,但早期组肿瘤细胞悬浮液中的 pDC 百分比明显更高。RCC 患者外周血中的中性粒细胞计数高于健康对照组,但两组肿瘤分期的中性粒细胞计数相似。晚期肿瘤中来自 CD45+细胞的中性粒细胞比例更高。与 PB 相比,肾癌细胞组织中 CD4+细胞的 Treg 比例更高,疾病分期之间无差异。我们的结果反映了免疫系统和肿瘤微环境中各种细胞之间的复杂相互作用。在疾病早期阶段,树突状细胞亚群的激活被外周和肿瘤组织中 T 调节细胞的早期出现所抵消。晚期阶段的特征是肿瘤中中性粒细胞的积累。适当的抗癌策略(尤其是免疫疗法)的时机应考虑到 RCC 患者免疫反应的这些动态。