Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Cancer Immunol Immunother. 2020 Oct;69(10):2009-2020. doi: 10.1007/s00262-020-02590-z. Epub 2020 May 12.
The subset distribution and immunophenotype of circulating immune cells ("peripheral blood immune cell profile") may reflect tumor development and response to cancer treatment. In order to use the peripheral blood immune cell profile as biomarker to monitor patients over time, it is crucial to know how immune cell subsets respond to therapeutic interventions. In this study, we investigated the effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma (CC).
The subset distribution and immunophenotype of T cells (CD3CD56), CD56 NK cells (CD3CD56), CD56 NK cells (CD3CD56) and NKT-like cells (CD3CD56) were studied in preoperative and postoperative peripheral blood mononuclear cell (PBMC) samples of 24 patients with CC by multiparameter flow cytometry. Changes in immunophenotype of circulating immune cells after tumor resection were studied in patients treated with and without (capecitabine-based) adjuvant therapy.
The NKT-like cell (% of total PBMCs) and CD8 T cell (% of total T cells) populations expanded in the peripheral blood of non-adjuvant-treated CC patients after surgery. NK- and NKT-like cells showed upregulation of activating receptors and downregulation of inhibitory receptors in non-adjuvant-treated CC patients after surgery. These changes were not observed in the peripheral blood of adjuvant-treated CC patients.
Our results suggest tumor-induced suppression of NK- and NKT-like cells in CC patients, an effect that could not be detected after tumor resection. In contrast, adjuvant therapy maintained tumor-induced immunosuppression of NK- and NKT-like cells in CC patients.
循环免疫细胞(“外周血免疫细胞谱”)的亚群分布和免疫表型可能反映肿瘤的发展和对癌症治疗的反应。为了将外周血免疫细胞谱用作随时间监测患者的生物标志物,了解免疫细胞亚群如何对治疗干预做出反应至关重要。在这项研究中,我们研究了结肠癌(CC)患者肿瘤切除和辅助治疗对其外周血免疫细胞谱的影响。
通过多参数流式细胞术研究了 24 例 CC 患者术前和术后外周血单个核细胞(PBMC)样本中 T 细胞(CD3CD56)、CD56 NK 细胞(CD3CD56)、CD56 NK 细胞(CD3CD56)和 NKT 样细胞(CD3CD56)的亚群分布和免疫表型。研究了接受和未接受(卡培他滨为基础)辅助治疗的 CC 患者肿瘤切除后循环免疫细胞免疫表型的变化。
未接受辅助治疗的 CC 患者手术后外周血中 NKT 样细胞(总 PBMC 的百分比)和 CD8 T 细胞(总 T 细胞的百分比)群体扩增。NK 和 NKT 样细胞在未接受辅助治疗的 CC 患者手术后上调激活受体,下调抑制受体。在接受辅助治疗的 CC 患者的外周血中未观察到这些变化。
我们的研究结果表明,CC 患者的肿瘤诱导性抑制 NK 和 NKT 样细胞,而手术后无法检测到这种效应。相比之下,辅助治疗维持了 CC 患者的肿瘤诱导性 NK 和 NKT 样细胞免疫抑制。