Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium
Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Int J Gynecol Cancer. 2019 Nov;29(9):1381-1388. doi: 10.1136/ijgc-2019-000521.
The behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.
In this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.
In a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.
Our immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.
免疫系统作为卵巢癌进展的驱动因素的行为几乎没有被研究过。我们的知识主要局限于肿瘤内适应性免疫系统。由于卵巢癌广泛转移,评估循环免疫系统似乎更准确。为了证明免疫细胞存在于卵巢肿瘤患者的血液样本中。
在这项探索性前瞻性队列研究中,从 143 名女性中采集了外周血单核细胞,其中包括 62 名良性囊肿患者、13 名交界性肿瘤患者、41 名侵袭性卵巢癌患者和 27 名年龄匹配的健康对照者。通过荧光激活细胞分选对基于 CD4(分化簇)、CD8、自然杀伤细胞、髓系来源的抑制细胞和调节性 T 细胞存在的免疫谱进行分析。
在多变量分析中,六种免疫细胞(活化的调节性 T 细胞、自然杀伤细胞、髓系来源的抑制细胞、单核细胞髓系来源的抑制细胞、耗竭的单核细胞髓系来源的抑制细胞和总髓细胞)被选为恶性肿瘤的独立预测因子,经矫正乐观性后,受体操作特征曲线下面积(AUC)为 0.858。相比之下,基于 CD8 和调节性 T 细胞的免疫谱,即卵巢癌免疫学中的当前标准,得出的 AUC 为 0.639。
我们在血液中的免疫谱表明,由髓系来源的抑制细胞驱动的先天免疫抑制参与了卵巢癌的发展。这一发现可能有助于患者的临床管理和免疫治疗的选择。