Clavijo-Salomon Maria A, Ramos Rodrigo N, Crippa Alexandre, Pizzo Celia R, Bergami-Santos Patricia C, Barbuto Jose Alexandre M
Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1730, São Paulo, SP, CEP 05508-900, Brazil.
Cancer Immunol Immunother. 2015 Feb;64(2):161-71. doi: 10.1007/s00262-014-1625-9. Epub 2014 Oct 15.
The chromophobe renal cell carcinoma (ChRCC), though associated with a hereditary cancer syndrome, has a good prognosis after tumor removal. The lack of recurrence could be related to the absence of immune system compromise in patients or to an effective functional recovery of immune functions after tumor removal. Thus, we evaluated monocyte-derived dendritic cells (Mo-DCs) in a 34-year-old male who had a ChRCC, before and after tumor removal.
CD14(+) monocytes from the patient's peripheral blood, 1 week before and 3 months after partial nephrectomy, were differentiated in vitro into immature and mature Mo-DCs. These were harvested, analyzed by flow cytometry and used as stimulators of allogeneic T cells. Supernatants from cultures were collected for cytokine analysis.
Tumor removal was associated with decreased expression of PD-L1, but also, surprisingly, of CD205, HLA-DR, CD80 and CD86 by Mo-DCs. Also, Mo-DC's ability to stimulate T cell proliferation increased, along with IL-2Rα expression and IFN-γ production. Simultaneously, the patients' Mo-DCs ability to induce Foxp3(+) T cells decreased after surgery. One-year postoperative follow-up shows no tumor recurrence.
The presence of a ChRCC affected Mo-DCs generated in vitro, which recovered their function after tumor removal. This indicates that the favorable outcome observed after ChRCC resection may be due to the restoration of immunocompetence. Furthermore, since functional alterations described for DCs within tumors may be also found in Mo-DCs, their accurate functional analysis-not restricted to the determination of their surface immunophenotype-may provide an indirect "window" to the tumor microenvironment.
嫌色性肾细胞癌(ChRCC)虽然与一种遗传性癌症综合征相关,但肿瘤切除后预后良好。缺乏复发可能与患者免疫系统未受损或肿瘤切除后免疫功能有效恢复有关。因此,我们评估了一名34岁患ChRCC男性患者在肿瘤切除前后单核细胞来源的树突状细胞(Mo-DC)。
在部分肾切除术前1周和术后3个月,从患者外周血中分离出CD14(+)单核细胞,在体外将其分化为未成熟和成熟的Mo-DC。收集这些细胞,通过流式细胞术进行分析,并用作异体T细胞的刺激物。收集培养上清液进行细胞因子分析。
肿瘤切除与Mo-DC上PD-L1的表达降低有关,但令人惊讶的是,CD205、HLA-DR、CD80和CD86的表达也降低。此外,Mo-DC刺激T细胞增殖的能力增强,同时伴有IL-2Rα表达和IFN-γ产生增加。同时,患者的Mo-DC诱导Foxp3(+) T细胞的能力在手术后下降。术后一年随访显示无肿瘤复发。
ChRCC的存在影响了体外生成的Mo-DC,肿瘤切除后其功能得以恢复。这表明ChRCC切除后观察到的良好结果可能归因于免疫能力的恢复。此外,由于肿瘤内DC的功能改变也可能在Mo-DC中发现,对其进行准确的功能分析(不限于确定其表面免疫表型)可能为肿瘤微环境提供一个间接的“窗口”。