NKG2D is a key receptor for recognition of bladder cancer cells by IL-2-activated NK cells and BCG promotes NK cell activation
NKG2D is a key receptor for recognition of bladder cancer cells by IL-2-activated NK cells and BCG promotes NK cell activation
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DOI：
10.3389/fimmu.2015.00284
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发表时间：
2015-06-08
影响因子：
7.3
通讯作者：
Vales-Gomez, Mar
中科院分区：
文献类型：
--
作者：
Maria Garcia-Cuesta, Eva;Lopez-Cobo, Sheila;Vales-Gomez, Mar
膀胱内灌注卡介苗（BCG）用于治疗浅表性膀胱癌，无论是乳头状肿瘤（经尿道切除后）还是高级扁平癌（原位癌），约70%的患者减少复发率。最初，卡介苗被提出通过炎症反应起作用，由分枝杆菌抗原的吞噬摄取和细胞因子释放介导。最近，其他免疫效应器如单核细胞、自然杀伤细胞（NK）和NKT细胞被认为在这种免疫反应中发挥作用。在这里，我们对多种膀胱癌细胞系作为免疫细胞的假定靶点进行了全面的研究，并评估了NK细胞在存在和不存在卡介苗的情况下对它们的识别。我们描述了不同的膀胱癌细胞可以表达多种NK细胞的激活和抑制配体。膀胱癌细胞的识别主要依赖于NKG2D， NKp46也有贡献。令人惊讶的是，暴露于卡介苗并没有影响膀胱细胞的免疫表型，也没有增加NK细胞对纯化的il -2激活细胞系的识别。然而，当混合淋巴细胞培养中加入卡介苗时，NK细胞被有效激活，这表明分枝杆菌治疗后NK细胞的激活需要多种免疫细胞的协同作用。我们还分析了一组接受卡介苗治疗的膀胱癌患者外周血NK细胞的百分比。NK细胞的总数在治疗过程中没有变化，这表明需要对肿瘤部位的NK细胞活化进行更详细的研究，以评估每位患者的反应。
Intravesical instillation of bacillus Calmette Guerin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.