Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Eur J Cancer. 2020 Aug;135:173-182. doi: 10.1016/j.ejca.2020.04.036. Epub 2020 Jun 23.
Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141), cDC2s (CD1c) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC).
Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets.
In both patient groups, the frequency of total CD141 DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141 DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival.
cDC1s are reduced in patients with OvC, and CD141 DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141 DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC.
树突状细胞（DCs）是最有效的抗原呈递细胞，因此能够引发强大且针对肿瘤的免疫反应。几十年来，人们一直在利用这种能力（主要使用单核细胞衍生的 DCs）来制定疫苗接种策略，但临床疗效有限。另一种选择是使用常规 DC（cDCs），其中至少有三个亚群在人类血液中循环：cDC1（CD141）、cDC2（CD1c）和浆细胞样 DC。尽管数量较少，但技术进步可能允许对其进行选择和临床应用。然而，关于 DC 亚群生物学的许多假设取决于对小鼠模型的观察，这阻碍了其转化潜力。在这项研究中，我们对卵巢癌（OvC）或前列腺癌（PrC）患者的人 DC 进行了特征描述。
对来自 OvC 或 PrC 患者和健康供体（HD）的全血样本进行流式细胞术评估，以对 DC 亚群进行表型和功能特征描述。
在两组患者中，总 CD141 DC 的频率均低于 HD，但仅 OvC 患者的 cDC1 亚群减少。CD141 DC 对 TLR3 激动剂 poly（I:C）的反应在两组患者中均降低。在 OvC 肿瘤负担标志物 CA125 与 cDC1 频率之间观察到负相关。在 OvC 组织（癌症基因组图谱数据集）中 CLEC9A 的高表达表明总生存期更好。
cDC1 减少存在于 OvC 患者中，CD141 DC 在 OvC 或 PrC 患者中无论是在数量上还是在质量上都受到损害。CD141 DC 的激活可能预示着功能受损。cDC1 的丢失可能是 OvC 患者的不良预后因素。
