Tumour immune microenvironment in primary and metastatic papillary renal cell carcinoma
Tumour immune microenvironment in primary and metastatic papillary renal cell carcinoma
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DOI：
10.1111/his.13987
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发表时间：
2019-12-11
期刊：
影响因子：
6.4
通讯作者：
Netto, George J.
中科院分区：
文献类型：
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作者：
Eich, Marie-Lisa;Chaux, Alcides;Netto, George J.
在肾细胞癌（RCC）中，肿瘤免疫微环境在透明细胞RCC中表现得最好。在这项研究中，我们研究了几种免疫标志物的表达，包括PD-L1，FoxP 3和CD 8在原发性和转移性乳头状肾细胞癌。方法和结果从1982年至2014年期间接受治疗的78例原发性乳头状RCC和配对转移性肿瘤（24例）中构建了三个组织微阵列。使用市售的PD-L1（克隆E1 L3 N）、FoxP 3、CD 8和Ki-67抗体进行免疫组织化学分析。肿瘤和/或相关免疫细胞中的标志物表达水平通过组织类型（非肿瘤与原发性肿瘤与转移性肿瘤）进行分析，并与临床病理学特征和结局相关。结论PD-L1在近四分之一的原发性和转移性乳头状肾细胞癌中表达。在单变量分析中，CD 8/FoxP 3比率>1与有利的结局相关，而具有大量CD 8/Ki-67双重阳性淋巴细胞的乳头状RCC显示肿瘤进展以及总体和癌症相关死亡率的可能性增加。在多变量分析中，当调整分期、分级和患者年龄时，CD 8/FoxP 3比值>1和CD 8/Ki-67高计数与预后的相关性仍然显著。
Aims Among renal cell carcinoma (RCC) the tumour immune microenvironment has been best characterised in clear cell RCC. In this study we investigated the expression of several immune markers, including PD-L1, FoxP3 and CD8 in primary and metastatic papillary RCC. Methods and results Three tissue microarrays were constructed from 78 cases with primary papillary RCC and paired metastatic tumour (24 cases) from 78 patients treated between 1982 and 2014. Immunohistochemistry analysis was performed using commercially available antibodies for PD-L1 (clone E1L3N), FoxP3, CD8 and Ki-67. Markers expression level in tumour and/or associated immune cells was analysed by tissue type (non-tumour versus primary tumour versus metastatic tumour) and correlated to clinicopathological features and outcome. Conclusion We found PD-L1 expression in up to one-quarter of primary and metastatic papillary RCC. On univariate analysis, CD8/FoxP3 ratio >1 was associated with favourable outcome, whereas papillary RCCs with high numbers of dual CD8/Ki-67-positive lymphocytes showed an increased likelihood for tumour progression and overall and cancer-related mortality. The association of CD8/FoxP3 ratio >1 and high count of CD8/Ki-67 with outcome remained significant on multivariate analysis when adjusting for stage, grade and patient's age.