Distinct expression patterns of Toll-like receptor 7 in tumour cells and fibroblast-like cells in oral squamous cell carcinoma
Distinct expression patterns of Toll-like receptor 7 in tumour cells and fibroblast-like cells in oral squamous cell carcinoma
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Toll样受体7在口腔鳞状细胞癌肿瘤细胞和成纤维细胞样细胞中的独特表达模式
DOI：
10.1111/his.12703
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发表时间：
2015-11-01
期刊：
影响因子：
6.4
通讯作者：
Hu, Qingang
中科院分区：
文献类型：
--
作者：
Ni, Yan Hong;Ding, Liang;Hu, Qingang
目的Toll样受体（TLR）-7激动剂已用于癌症免疫治疗，但肿瘤异质性意味着TLR-7活性在肿瘤微环境的不同组分中是可变的，并且口腔鳞状细胞癌（OSCC）中TLR-7的特征尚不清楚。方法和结果二十个健康口腔组织，对50例口腔白斑组织和166例回顾性原发性口腔鳞癌组织进行TLR-7免疫组化染色，结果显示TLR-7在口腔白斑癌变过程中表达上调。此外，肿瘤细胞（TC）中TLR-7高表达的患者分化和预后较差。有趣的是，TLR-7在基质成纤维细胞样细胞（FLC）中高表达的患者具有低肿瘤分期，无淋巴结转移（LNM）和更好的预后。此外，评估Ki-67、CD 3、CD 4、CD 8和叉头盒蛋白3（FoxP 3）（+）肿瘤浸润的淋巴细胞，我们发现TLR-7（高）TC由较少的CD 3（+）CD 4（+）但较多的FoxP 3（+）淋巴细胞浸润。重要的是，TLR-7（低）TC和TLR-7（高）FLC患者比TLR-7（高）TC/TLR-7（低）FLC患者FoxP 3（+）淋巴细胞浸润更少，生存时间更长，尽管TLR-7不是OSCC的独立预后因素。间质FLC可能适合TLR-7激动剂的免疫治疗。
AimsToll-like receptor (TLR)-7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR-7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR-7 in oral squamous cell carcinoma (OSCC) are unclear.Methods and resultsTwenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR-7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR-7 in tumour cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR-7 in stroma fibroblast-like cells (FLCs) had low tumour stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, Ki-67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)(+) tumour-infiltrated lymphocytes were assessed and we found that TLR-7(high) TCs were infiltrated by fewer CD3(+)CD4(+) but more FoxP3(+) lymphocytes. Importantly, patients with TLR-7(low)TCs and TLR-7(high)FLCs had less FoxP3(+) lymphocyte infiltration and longer survival time than those with TLR-7(high)TCs/TLR-7(low)FLCs, although TLR-7 was not an independent prognostic factor for OSCC.ConclusionsThe low expression of TLR-7 in tumour and high expression of TLR-7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR-7 agonist.